bims-kracam Biomed News
on K-Ras in cancer metabolism
Issue of 2022–03–06
93 papers selected by
Yasmin Elkabani, Egyptian Foundation for Research and Community Development
  1. Polymeric nanomicelles of curcumin: Potential applications in cancer.
  2. Carrier Free O2 -Economizer for Photodynamic Therapy Against Hypoxic Tumor by Inhibiting Cell Respiration.
  3. Potential anticancer properties and mechanisms of thymoquinone in osteosarcoma and bone metastasis.
  4. Photothermal combined with intratumoral injection of annonaceous acetogenin nanoparticles for breast cancer therapy.
  5. Apoptosis Triggering, an Important Way for Natural Products From Herbal Medicines to Treat Pancreatic Cancers.
  6. ROS-Activated Nanoscale Coordination Polymers for Enhanced Ultrasound-mediated Therapy for the Treatment of Cancer.
  7. Drug Delivery Systems for Photodynamic Therapy: The Potentiality and Versatility of Electrospun Nanofibers.
  8. Recent advances in glycyrrhizin metabolism, health benefits, clinical effects and drug delivery systems for efficacy improvement; a comprehensive review.
  9. A silica-based antioxidant nanoparticle for oral delivery of Camptothecin which reduces intestinal side effects while improving drug efficacy for colon cancer treatment.
  10. Light amplified oxidative stress in tumor microenvironment by carbonized hemin nanoparticles for boosting photodynamic anticancer therapy.
  11. Targeted delivery of albumin nanoparticles for breast cancer: A review.
  12. The chemistry, processing, and preclinical anti-hyperuricemia potential of tea: a comprehensive review.
  13. Research Progress and Prospects for Polymeric Nanovesicles in Anticancer Drug Delivery.
  14. Look into my onco-forest - review of plant natural products with anticancer activity.
  15. Crosstalk between ferroptosis and the epithelial-mesenchymal transition: Implications for inflammation and cancer therapy.
  16. Ferroptosis in hematological malignancies and its potential network with abnormal tumor metabolism.
  17. Targeting ASCT2-mediated Glutamine Metabolism Inhibits Proliferation and Promotes Apoptosis of Pancreatic Cancer cell.
  18. Dendrimer-Based Nanomedicine (Paramagnetic Nanoparticle, Nanocombretastatin, Nanocurcumin) for Glioblastoma Multiforme Imaging and Therapy.
  19. Insulin and cancer: a tangled web.
  20. Journey of Alpinia galanga from kitchen spice to nutraceutical to folk medicine to nanomedicine.
  21. Frankincense diterpenes as a bio-source for drug discovery.
  22. Microneedle-Mediated Transdermal Delivery of Drug-Carrying Nanoparticles.
  23. Flavonoids, anthocyanins, betalains, curcumin, and carotenoids: Sources, classification and enhanced stabilization by encapsulation and adsorption.
  24. Fabrication of Laponite-Reinforced Dextran-Based Hydrogels for NIR-Responsive Controlled Drug Release.
  25. pH-sensitive hyaluronic acid-targeted prodrug micelles constructed via a one-step reaction for enhanced chemotherapy.
  26. Protective effects of functional foods against Parkinson's disease: A narrative review on pharmacology, phytochemistry, and molecular mechanisms.
  27. Recent Progress in Nanostructured Smart Drug Delivery Systems for Cancer Therapy: A Review.
  28. Multifunctional photodynamic/photothermal nano-agents for the treatment of oral leukoplakia.
  29. Current research status of alkaloids against breast cancer.
  30. Progress in the Mechanism of Autophagy and Traditional Chinese Medicine Herb Involved in Dementia.
  31. Reprogramming hormone sensitive prostate cancer to a lethal neuroendocrine cancer lineage by mitochondrial pyruvate carrier (MPC).
  32. Asymmetric, amphiphilic RGD conjugated phthalocyanine for targeted photodynamic therapy of triple negative breast cancer.
  33. A Review on Curcumin-Loaded Electrospun Nanofibers and their Application in Modern Medicine.
  34. Ultrasound versus Light: Exploring Photophysicochemical and Sonochemical Properties of Phthalocyanine-Based Therapeutics, Theoretical Study, and In Vitro Evaluations.
  35. Development and optimization of curcumin analog nano-bilosomes using 21.31 full factorial design for anti-tumor profiles improvement in human hepatocellular carcinoma: in-vitro evaluation, in-vivo safety assay.
  36. Nanomedicine of Plant Origin for the Treatment of Metabolic Disorders.
  37. Double-crosslinked bifunctional hydrogels with encapsulated anti-cancer drug for bone tumor cell ablation and bone tissue regeneration.
  38. Are we still on the right Path(way)?: the altered expression of the pentose phosphate pathway in solid tumors and the potential of its inhibition in combination therapy.
  39. Mitochondria-Targeting Chemodynamic Therapy Nanodrugs for Cancer Treatment.
  40. The histidine phosphatase LHPP: an emerging player in cancer.
  41. Therapeutic Potential of Glutamine Pathway in Lung Cancer.
  42. Targeting nanoparticles to malignant tumors.
  43. Fabrication and Assessment of Diosgenin Encapsulated Stearic Acid Solid Lipid Nanoparticles for Its Anticancer and Antidepressant Effects Using in vitro and in vivo Models.
  44. Zerumbone-induced reactive oxygen species-mediated oxidative stress re-sensitizes breast cancer cells to paclitaxel.
  45. Re-establishing the comprehension of phytomedicine and nanomedicine in inflammation-mediated cancer signaling.
  46. Harnessing the therapeutic potential of fisetin and its nanoparticles: Journey so far and road ahead.
  47. Phytocompounds from the medicinal and dietary plants: Multi-target agents for cancer prevention and therapy.
  48. Silent mutations reveal therapeutic vulnerability in RAS Q61 cancers.
  49. Biomimetic Cucurbitacin B-Polydopamine Nanoparticles for Synergistic Chemo-Photothermal Therapy of Breast Cancer.
  50. Autophagy and cancer: Can tetrandrine be a potent anticancer drug in the near future?
  51. Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis treatment.
  52. Recent advances in targeted drug delivery for the treatment of pancreatic ductal adenocarcinoma.
  53. [Research progress about photothermal nanomaterials with targeted antibacterial properties and their applications in wound healing].
  54. Theranostic nanoplatforms of emodin-chitosan with blue laser light on enhancing the anti-biofilm activity of photodynamic therapy against Streptococcus mutans biofilms on the enamel surface.
  55. Mesoporous silica nanoparticle-supported nanocarriers with enhanced drug loading, encapsulation stability, and targeting efficiency.
  56. Docetaxel and 5-FU enhanced the inhibitory effects of apatinib and ramucirumab on growth and migration of gastric cancer.
  57. Ethnomedical, phytochemical and pharmacological insights on an Indian medicinal plant: The balloon vine (Cardiospermum halicacabum Linn.).
  58. Ferroptosis: An emerging therapeutic opportunity for cancer.
  59. Controlled release of 5-fluorouracil to melanoma cells using a hydrogel/micelle composites based on deoxycholic acid and carboxymethyl chitosan.
  60. A Review: Potential Application and Outlook of Photothermal Therapy in Oral Cancer Treatment.
  61. A review on the potential use of natural products in overweight and obesity.
  62. Shielded geomagnetic field accelerates glucose consumption in human neuroblastoma cells by promoting anaerobic glycolysis.
  63. Potential applications of cocoa (Theobroma cacao) on diabetic neuropathy: mini-review.
  64. Anticancer nanomedicines harnessing tumor microenvironmental components.
  65. Bioactive compounds: Application of albumin nanocarriers as delivery systems.
  66. Immunogenic nanomedicine based on GSH-responsive nanoscale covalent organic polymers for chemo-sonodynamic therapy.
  67. The ascension of nanosponges as a drug delivery carrier: preparation, characterization, and applications.
  68. Stilbenes: Characterization, bioactivity, encapsulation and structural modifications. A review of their current limitations and promising approaches.
  69. Recent Advances in Nanoplatforms for the Treatment of Osteosarcoma.
  70. A mathematical model for imaging and killing cancer cells by using concepts of the Warburg effect in designing a Graphene system.
  71. pH-Sensitive Bioprobe for Multichannel Mitochondrial Imaging and Photodynamic Therapy.
  72. The Apoptosis of Liver Cancer Cells Promoted by Curcumin/TPP-CZL Nanomicelles With Mitochondrial Targeting Function.
  73. Ferroptosis as a novel form of regulated cell death: Implications in the pathogenesis, oncometabolism and treatment of human cancer.
  74. Dual functions of epigallocatechin gallate surface-modified Au nanorods@selenium composites for near-infrared-II light-responsive synergistic antibacterial therapy.
  75. Synergistic photodynamic/photothermal bacterial inactivation over heterogeneous quaternized chitosan/silver/cobalt phosphide nanocomposites.
  76. Intranasal Niosomal in situ Gel as a Novel Strategy for Improving Citicoline Efficacy and Brain Delivery in Treatment of Epilepsy: In vitro and ex vivo characterization and in vivo pharmacodynamics investigation.
  77. Advanced metal and carbon nanostructures for medical, drug delivery and bio-imaging applications.
  78. Formulation Strategies and Therapeutic Applications of Shikonin and Related Derivatives.
  79. Phytochemical profile and biological activities of Bromelia antiacantha extracts.
  80. Cannabidiol and Other Phytocannabinoids as Cancer Therapeutics.
  81. Review On Different Vesicular Drug Delivery Systems (VDDSs) And Their Applications.
  82. Dietary Polyphenols and Their Role in Oxidative Stress-Induced Human Diseases: Insights Into Protective Effects, Antioxidant Potentials and Mechanism(s) of Action.
  83. Phosphatidylserine liposomes containing curcumin inhibit bone loss in osteoporotic rats: A possible synergy through a common signaling pathway.
  84. Cancer epigenetics: promises and pitfalls for cancer therapy.
  85. The science of resveratrol, formulation, pharmacokinetic barriers and its chemotherapeutic potential.
  86. Enzyme-mediated intratumoral self-assembly of nanotheranostics for enhanced imaging and tumor therapy.
  87. Nano to rescue: repository of nanocarriers for targeted drug delivery to curb breast cancer.
  88. Stimuli-sensitive drug delivery systems for site-specific antibiotic release.
  89. Glucose Influences the Response of Glioblastoma Cells to Temozolomide and Dexamethasone.
  90. Cinnamon could improve hepatic steatosis caused by a high-fat diet via enhancing hepatic beta-oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation in male rats.
  91. Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.
  92. Hybrid Cell Membrane-Functionalized Biomimetic Nanoparticles for Targeted Therapy of Osteosarcoma.
  93. Distinct roles of glutamine metabolism in benign and malignant cartilage tumors with IDH mutations.
  1. Int J Pharm. 2022 Feb 26. pii: S0378-5173(22)00177-6. [Epub ahead of print]617 121622
    Polymeric nanomicelles of curcumin: Potential applications in cancer.
    Leila Farhoudi, Prashant Kesharwani, Muhammed Majeed, Thomas P Johnston, Amirhossein Sahebkar.
      Natural compounds, primarily derived from plants, have been isolated and evaluated as alternative and complementary treatments for cancer. Curcumin has been proven to be beneficial in cancer therapy due to its multiple effects on cell signaling pathways, although the application of curcumin is limited due to its low oral bioavailability. Nanotechnology-based drug delivery systems have been used to overcome limited bioavailability and ensure greater biodistribution after administration. Nano-formulations of curcumin have shown more significant anticancer activity than free curcumin. Among the various nanocarriers, polymeric micelles with inherent stability and ease of formulation are ideal for tumor targeting via the enhanced permeation and retention (EPR) effect. The structure of polymeric micelles is suitable for the encapsulation of hydrophobic or low water-soluble drugs. Additionally, the outer shell of polymeric micelles provides protection against the normal uptake of foreign compounds by the reticuloendothelial system (RES). This review discusses the recent developments in curcumin delivery using polymeric micelles for various cancers.
    Keywords:  Cancer; Curcumin; Nanocarriers; Nanotechnology; Natural compounds; Oral bioavailability; Polymeric micelles
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.121622
  2. Small. 2022 Feb 27. e2107467
    Carrier Free O2 -Economizer for Photodynamic Therapy Against Hypoxic Tumor by Inhibiting Cell Respiration.
    Jia-Qi Huang, Lin-Ping Zhao, Xiang Zhou, Ling-Shan Liu, Rong-Rong Zheng, Fu-An Deng, Yi-Bin Liu, Xi-Yong Yu, Shi-Ying Li, Hong Cheng.
      Abnormal tumor metabolism causes the hypoxic microenvironment, which greatly limits the efficacy of photodynamic therapy (PDT). In this work, a strategy of metabolic reprogramming is proposed to economize O2 for enhanced PDT against hypoxic tumors. The carrier-free O2 -economizer (designated as LonCe) is prepared based on the metabolic antitumor drug of Lonidamine (Lon) and the photosensitizer of chlorin e6 (Ce6). By virtue of intermolecular interactions, Lon and Ce6 self-assemble into nanosized LonCe with favorable stability and high drug contents. Compared with Ce6, LonCe exhibits an improved cellular uptake and photodynamic property for tumor treatment. Moreover, LonCe is capable of inhibiting cell metabolism and mitochondrial respiration to remit the tumor hypoxia, which would promote reactive oxygen species (ROS) production and elevate the PDT efficacy on tumor suppression. In vivo experiments indicate that intravenously injected LonCe prefers to accumulate at the tumor site for highly efficient PDT regardless of the hypoxic environment. Besides, the self-delivery LonCe is fabricated without any carriers, which avoids the excipients induced system toxicity and immunogenicity in vivo. This carrier-free nanomedicine with cell respiratory inhibition mechanism would expedite the development and clinical translation of photodynamic nanoplatforms in tumor treatment.
    Keywords:  carrier free O 2-economizer; cell respiration; hypoxia; nanomedicine; photodynamic therapy
    DOI:  https://doi.org/10.1002/smll.202107467
  3. Cell Mol Biol Lett. 2022 Mar 02. 27(1): 21
    Potential anticancer properties and mechanisms of thymoquinone in osteosarcoma and bone metastasis.
    Mina Homayoonfal, Zatollah Asemi, Bahman Yousefi.
      Despite great advances, therapeutic approaches of osteosarcoma, the most prevalent class of preliminary pediatric bone tumors, as well as bone-related malignancies, continue to demonstrate insufficient adequacy. In recent years, a growing trend toward applying natural bioactive compounds, particularly phytochemicals, as novel agents for cancer treatment has been observed. Bioactive phytochemicals exert their anticancer features through two main ways: they induce cytotoxic effects against cancerous cells without having any detrimental impact on normal cell macromolecules such as DNA and enzymes, while at the same time combating the oncogenic signaling axis activated in tumor cells. Thymoquinone (TQ), the most abundant bioactive compound of Nigella sativa, has received considerable attention in cancer treatment owing to its distinctive properties, including apoptosis induction, cell cycle arrest, angiogenesis and metastasis inhibition, and reactive oxygen species (ROS) generation, along with inducing immune system responses and reducing side effects of traditional chemotherapeutic drugs. The present review is focused on the characteristics and mechanisms by which TQ exerts its cytotoxic effects on bone malignancies.
    Keywords:  Angiogenesis; Apoptosis; Bone metastasis; Chemotherapy resistance; Osteosarcoma; Signaling pathway; Thymoquinone
    DOI:  https://doi.org/10.1186/s11658-022-00320-0
  4. Colloids Surf B Biointerfaces. 2022 Feb 23. pii: S0927-7765(22)00109-6. [Epub ahead of print]213 112426
    Photothermal combined with intratumoral injection of annonaceous acetogenin nanoparticles for breast cancer therapy.
    Cuiling Zuo, Yuan Zou, Guangyu Gao, Lina Sun, Bo Yu, Yifei Guo, Xiangtao Wang, Meihua Han.
      ACGs (annonaceous acetogenins) possess excellent antitumor activity, but their serious accompanying toxicity has prevented their application in the clinic. To address this problem, we therefore constructed an intratumoral drug delivery system integrating chemotherapy and photothermal therapy. The PEGylation of polydopamine nanoparticles (PDA-PEG NPs) possessed an excellent biocompatibility with size of 70.96 ± 2.55 nm, thus can be used as good photothermal materials in the body. Moreover, PDA-PEG NPs can kill half of cancer cells under NIR (near-infrared) laser irradiation, and the survival rate of 4T1 cells is only 1% when ACG NPs and PDA-PEG NPs are combined. In vivo distribution studies showed that the 0.1 mg/kg ACGs NPs + PDA-PEG NPs + NIR group had the highest tumor inhibition rate, which was significantly superior to that of the 0.1 mg/kg ACGs NPs intratumoral injection group (82.65% vs. 59.08%). Altogether, the combination of PDA-PEG NPs + NIR with chemotherapy drugs may provide a feasible and effective strategy for the treatment of superficial tumors.
    Keywords:  Annonaceous acetogenins; Breast cancer; Intratumor injection; Photothermal therapy; Polydopamine
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112426
  5. Front Pharmacol. 2021 ;12 796300
    Apoptosis Triggering, an Important Way for Natural Products From Herbal Medicines to Treat Pancreatic Cancers.
    Meiyan Li, Dandan Tang, Ting Yang, Die Qian, Runchun Xu.
      Pancreatic cancer, a poor prognosis and high morbidity and mortality cancer, is a malignant tumor occurring in pancreatic exocrine glands. Currently, surgery and gemcitabine (Gem) are commonly used to treat pancreatic cancers. However, the high recurrence rate and resistance makes the therapeutic effects still unsatisfied. Apoptosis is comprehensively recognized as one of the major ways of the programmed cell death, refers to the autonomous and orderly death process of cells in order to maintain the stability of the body's environment after receiving a certain signal or stimulation. Currently, it has also been proven to be a promising way for the treatment of pancreatic cancer. Nowadays, some active ingredients from herbal medicine have been reported to be effective for the treatment of pancreatic cancer via inducing cells apoptosis. Therefore, this article reviews the current references regarding anti pancreatic cancer effects of natural products derived from herbal medicines via triggering apoptosis, and summarizes the related potential signal pathways, including death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, MAPK mediated apoptotic pathway, ERS mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other pathways such as JAK-STAT signal pathway, which can lay a certain foundation for the research and development of new natural products against pancreatic cancer.
    Keywords:  apoptosis; herbal medicine; natural products; pancreatic cancer; signal pathways
    DOI:  https://doi.org/10.3389/fphar.2021.796300
  6. Acta Biomater. 2022 Feb 24. pii: S1742-7061(22)00113-1. [Epub ahead of print]
    ROS-Activated Nanoscale Coordination Polymers for Enhanced Ultrasound-mediated Therapy for the Treatment of Cancer.
    Jianming Zhao, Jirong Shi, Xiangdan Meng, Chenchen Gong, Peng Wu, Zhou Yang, Haifeng Dong.
      Stimuli-responsive nanoplatforms for efficient delivery of drugs in an on-demand manner show promising potential for killing cancer cells with high accuracy and minimal invasiveness. Herein, taking advantage of the good tissue-penetrating depth of sonodynamic therapy (SDT), reactive oxygen species (ROS)-responsive nanoscale coordination polymers (NCPs) were designed through self-assembly of porphyrins (PP) and platinum, which contained ROS-cleavable thioketal (TK) linkers to enhance the release of doxorubicin (Dox) during SDT. Upon exposure to the ultrasound (US), the Dox-loaded NCPs (PTK@PEG/Dox) could generate high amounts of cytotoxic ROS and heat, which not only induced the apoptosis of MCF-7 cells but also facilitated the efficient release of Dox due to the decomposition of the ROS-sensitive TK linkers, achieving the synergistic therapy of US-induced therapy and chemotherapy. After being modified with Arg-Gly-Asp (RGD) peptide, RGD/PTK@PEG exhibited a good targeting ability to cancer cells. Importantly, using the multicellular tumor spheroids (MCTS) derived from MCF-7 cells as a model, the RGD/PTK@PEG/Dox exhibited an efficient and controlled release behavior of Dox under the US irradiation, accompanying a tremendous anti-cancer effect for inducing apoptosis in the solid tumor tissues. This work provided a potential strategy to design controllable and stimuli-responsive nanoplatforms for synergistic/enhanced US-induced cancer therapy. STATEMENT OF SIGNIFICANCE: Stimulus-responsive nanoplatforms can deliver drugs efficiently in an on-demand manner, showing the potential to kill cancer cells with high accuracy and minimal invasiveness. Taking advantage of the good penetration ability of ultrasound (US), nanoscale coordination polymers (NCP) composed of porphyrin (PP), thioketal (TK) linkers, and platinum(II) were prepared via a coordination-driven self-assembly procedure. After doxorubicin (Dox) was loaded on the NCP (PTK@PEG/Dox), the nanoplatform responded to reactive oxygen species (ROS) under the stimulation of US, and induced the on-demand release of Dox, thereby achieving the combined therapeutic effect of sonodynamic therapy (SDT) and chemotherapy for cancer. This work provides a potential strategy for the development of controllable and stimuli-responsive nanoplatforms for enhanced ultrasound-induced cancer therapy. Introduction.
    Keywords:  ROS-sensitive cleavage; drug delivery; nanoscale coordination polymers; sonodynamic therapy; synergistic therapy
    DOI:  https://doi.org/10.1016/j.actbio.2022.02.030
  7. Macromol Biosci. 2022 Mar 05. e2100512
    Drug Delivery Systems for Photodynamic Therapy: The Potentiality and Versatility of Electrospun Nanofibers.
    Sofia M Costa, Raul Fangueiro, Diana P Ferreira.
      Recently, photodynamic therapy (PDT) has become a promising approach for the treatment of a broad range of diseases, including oncological and infectious diseases. This minimally invasive and localized therapy is based on the production of reactive oxygen species (ROS) able to destroy cancer cells and inactivate pathogens by combining the use of photosensitizers (PSs), light and molecular oxygen. To overcome the drawbacks of drug systemic administration, drug delivery systems (DDS) can be used to carrier the PSs, allowing higher therapeutic efficacy and minimal toxicological effects. Polymeric nanofibers produced by electrospinning emerged as powerful platforms for drug delivery applications. Electrospun nanofibers exhibit outstanding characteristics, such as large surface area to volume ratio associated with high drug loading, high porosity, flexibility, ability to incorporate and release a wide variety of therapeutic agents, biocompatibility and biodegradability. Due to the versatility of this technique, fibers with different morphologies and functionalities, including drug release profile can be produced. The possibility of scalability makes electrospinning even more attractive for the development of DDS. This review aims to explore and show an up to date of the huge potential of electrospun nanofibers as DDS for different PDT applications and discuss the opportunities and challenges in this field. This article is protected by copyright. All rights reserved.
    Keywords:  biodegradable polymers; cancer; drug delivery systems; electrospun nanofibers; infections; photodynamic therapy
    DOI:  https://doi.org/10.1002/mabi.202100512
  8. Phytomedicine. 2022 Feb 19. pii: S0944-7113(22)00077-0. [Epub ahead of print]99 153999
    Recent advances in glycyrrhizin metabolism, health benefits, clinical effects and drug delivery systems for efficacy improvement; a comprehensive review.
    Alaa F Bakr, Ping Shao, Mohamed A Farag.
       BACKGROUND: Glycyrrhizin (GL) is a major active constituent of licorice root (Glycyrrhiza glabra) that is considered one of the oldest and most frequently employed botanicals in Chinese medicine and worldwide, with most effects attributed to its rich GL content. Structurally, GL a triterpene saponin that is widely used as a flavoring agent in foodstuffs and cosmetics, and also proposed for various clinical applications with a myriad of health benefits. Pharmacological and biological activities of GL include antiviral, anti-inflammatory, antioxidant, and anticancer activities (in vitro and in vivo). Currently, there is no comprehensive review on GL biological effects and its action mechanisms.
    PURPOSE: This review summarizes GL pharmacological actions from a molecular biology perception, presented on its metabolism and side effects based on in vitro, in vitro and clinical studies. Moreover, the potential of GL as a nanomedicine delivery system is also summarized. The progress in drug delivery research using GL presented herein is expected to provide a theoretical basis for developing other novel drugs formulations.
    METHODS: A systematic review was carried out in several electronic databases (Science Direct, SpringerLink, CNKI, PubMed, Web of Science, Elsevier, and Scopus), using the following key words: glycyrrhizin "AND" bioactivity "OR" clinic "OR" therapeutic "OR" drug delivery. This search included manuscripts published between 1989 and 2021.
    RESULTS: 126 researches were selected and summarized in this review. The analysis of these studies indicated that GL has antiviral activity against different viruses. Further, GL efficiently suppressed the respiratory manifestations associated with COVID-19 by reducing the expression of angiotensin converting enzyme 2 (ACE2) that employed by the virus as an entry point. Otherwise, GL was found to induce antioxidant, anti-inflammatory, immune-modulatory, and anticancer activity. Besides, diminution the particle size of GL to nanometer size significantly augments their action and biodistribution.
    CONCLUSION: This article summarizes the pharmacological actions of GL. The potential of GL as a nanomedicine delivery system is also presented. Nevertheless, most studies reported provide no deep insight of GL health effects warranting for more future studies to elucidate its action mechanism and potential therapeutic benefits through preclinical and clinical trials.
    Keywords:  Anti-inflammatory; Anticancer; Antioxidant; Antiviral; Glycyrrhizin; Nanocarrier delivery system
    DOI:  https://doi.org/10.1016/j.phymed.2022.153999
  9. Acta Biomater. 2022 Feb 27. pii: S1742-7061(22)00119-2. [Epub ahead of print]
    A silica-based antioxidant nanoparticle for oral delivery of Camptothecin which reduces intestinal side effects while improving drug efficacy for colon cancer treatment.
    Quynh Nhu Nguyen-Trinh, Kim Xuyen Thi Trinh, Nhu-Thuy Trinh, Van Toi Vo, Nan Li, Yukio Nagasaki, Long Binh Vong.
      Camptothecin (CPT) is a potent anticancer agent for the treatment of colorectal cancer; however, it exhibits some limitations, including poor solubility, low stability, and low bioavailability via oral administration, which restrict its usability in clinical treatments. In addition, overproduction of reactive oxygen species (ROS) during chemotherapy induces drug resistance and severe intestinal side effects. In this study, silica-installed ROS scavenging nanoparticles (siRNP) with 50-60 nm in diameter were employed to overcome the aforementioned drawbacks of CPT. The solubility of CPT was significantly improved by incorporating it into the core of the nanoparticle, forming CPT-loaded siRNP (CPT@siRNP). The anticancer activity of CPT@siRNP against colorectal cancer cells (C-26) in vitro was significantly improved as compared to free CPT through higher efficiency of intracellular internalization and induction of apoptosis. Owing to its antioxidant properties, CPT@siRNP reduced cytotoxicity to normal endothelial cells, which was in sharp contrast to the high toxicity of free CPT. Oral administration of CPT and CPT@siRNP to the C-26 tumor-bearing mice exhibited antitumor activity, accompanied by effective suppression of tumor growth. Although CPT treatment suppressed tumor progression, it caused severe side effects, including intestinal damage and significant bodyweight loss. Interestingly, such noticeable side effects were not observed in the mice treated with CPT@siRNP, and the effect of tumor growth inhibition tended to be similar to or higher than that of CPT treatment. The results obtained in this study indicate that CPT@siRNP is a potential therapeutic nanomedicine for the treatment of colon cancer. STATEMENT OF SIGNIFICANCE: Here we employed silica-containing antioxidant nanoparticle (siRNP) as promising oral delivery nanocarrier of campothecine (CPT) to treat colon cancer. The design of siRNP via covalent conjugation of antioxidant nitroxide radicals and the silanol groups in the polymer backbone contributes to a significant increase in the absorption of hydrophobic drug molecules inside the core and enhances the stability of nanoparticles in the gastrointestinal environment for oral drug delivery. CPT-loaded siRNP (CPT@siRNP) significantly improved solubility of CPT. As compared to free CTP, the CPT@siRNP treatment showed a significantly higher toxicity to colon cancer cell, inhibition of cancer cell migration, and induction of apopotosis. With the antioxidant feature, siRNP also significantly suppressed the intestinal side effects caused by CPT treatment in tumor-bearing mouse model.
    Keywords:  Camptothecin; TEMPO; cancer chemotherapy; drug delivery system; nitroxide radical; reactive oxygen species (ROS); redox nanoparticles
    DOI:  https://doi.org/10.1016/j.actbio.2022.02.036
  10. Light Sci Appl. 2022 Mar 01. 11(1): 47
    Light amplified oxidative stress in tumor microenvironment by carbonized hemin nanoparticles for boosting photodynamic anticancer therapy.
    Liyun Lin, Wen Pang, Xinyan Jiang, Shihui Ding, Xunbin Wei, Bobo Gu.
      Photodynamic therapy (PDT), which utilizes light excite photosensitizers (PSs) to generate reactive oxygen species (ROS) and consequently ablate cancer cells or diseased tissue, has attracted a great deal of attention in the last decades due to its unique advantages. However, the advancement of PDT is restricted by the inherent characteristics of PS and tumor microenvironment (TME). It is urgent to explore high-performance PSs with TME regulation capability and subsequently improve the therapeutic outcomes. Herein, we reported a newly engineered PS of polymer encapsulated carbonized hemin nanoparticles (P-CHNPs) via a facile synthesis procedure for boosting photodynamic anticancer therapy. Solvothermal treatment of hemin enabled the synthesized P-CHNPs to enhance oxidative stress in TME, which could be further amplified under light irradiation. Excellent in vitro and in vivo PDT effects were achieved due to the improved ROS (hydroxyl radicals and singlet oxygen) generation efficiency, hypoxia relief, and glutathione depletion. Moreover, the superior in vitro and in vivo biocompatibility and boosted PDT effect make the P-CHNPs a potential therapeutic agent for future translational research.
    DOI:  https://doi.org/10.1038/s41377-021-00704-5
  11. Colloids Surf B Biointerfaces. 2022 Feb 23. pii: S0927-7765(22)00105-9. [Epub ahead of print]213 112422
    Targeted delivery of albumin nanoparticles for breast cancer: A review.
    Shalvi Sinai Kunde, Sarika Wairkar.
      Breast cancer has been identified as one of the most common cancers diagnosed in women. Various nanotechnology platforms offering unique features are considered in breast cancer treatment. Albumin is a versatile biodegradable, biocompatible, non-toxic and non-immunogenic protein nanocarrier. These characteristics attracted strong attention to fabricate albumin nanoparticles to deliver chemotherapeutic agents without major adverse effects. Albumin nanoparticles can undergo surface modifications using different ligands promoting tumor-targeted drug delivery. Moreover, multifunctional albumin nanoparticle is an upcoming strategy to attain efficient cancer therapy. This review gives an account of the potential albumin nanoparticles developed for chemotherapeutic drug delivery and its targeted approach for breast cancer. It also covers different multifunctional therapies available using albumin nanoparticles as breast cancer theranostics.
    Keywords:  Albumin nanoparticles; Bovine serum albumin; Breast cancer; Human serum albumin; Targeted delivery
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112422
  12. Crit Rev Food Sci Nutr. 2022 Mar 03. 1-26
    The chemistry, processing, and preclinical anti-hyperuricemia potential of tea: a comprehensive review.
    Yu Chen, Liyong Luo, Shanshan Hu, Renyou Gan, Liang Zeng.
      Hyperuricemia is an abnormal purine metabolic disease that occurs when there is an excess of uric acid in the blood, associated with cardiovascular diseases, hypertension, gout, and renal disease. Dietary intervention is one of the most promising strategies for preventing hyperuricemia and controlling uric acid concentrations. Tea (Camellia sinensis) is known as one of the most common beverages and the source of dietary polyphenols. However, the effect of tea on hyperuricemia is unclear. Recent evidence shows that a lower risk of hyperuricemia is associated with tea intake. To better understand the anti-hyperuricemia effect of tea, this review first briefly describes the pathogenesis of hyperuricemia and the processing techniques of different types of tea. Next, the epidemiological and experimental studies of tea and its bioactive compounds on hyperuricemia in recent years were reviewed. Particular attention was paid to the anti-hyperuricemia mechanisms targeting the hepatic uric acid synthase, renal uric acid transporters, and intestinal microbiota. Additionally, the desirable intake of tea for preventing hyperuricemia is provided. Understanding the anti-hyperuricemia effect and mechanisms of tea can better utilize it as a preventive dietary strategy.HighlightsHigh purine diet, excessive alcohol/fructose consumption, and less exercise/sleep are the induction factors of hyperuricemia.Tea and tea compounds showed alleviated effects for hyperuricemia, especially polyphenols.Tea (containing caffeine or not) is not associated with a higher risk of hyperuricemia.Xanthine oxidase inhibition (reduce uric acid production), Nrf2 activation, and urate transporters regulation (increase uric acid excretion) are the potential molecular targets of anti-hyperuricemic effect of tea.About 5 g tea intake per day may be beneficial for hyperuricemia prevention.
    Keywords:  Hyperuricemia; health effects; metabolic disorders; phytochemicals; tea; tea biochemistry
    DOI:  https://doi.org/10.1080/10408398.2022.2040417
  13. Front Bioeng Biotechnol. 2022 ;10 850366
    Research Progress and Prospects for Polymeric Nanovesicles in Anticancer Drug Delivery.
    Dan Li, Xi Zhang, Xiao Chen, Wei Li.
      Polymeric vesicles served as the most promising candidates of drug delivery nanocarriers are attracting increasing attention in cancer therapy. Significant advantages have been reported, including hydrophilic molecules with high loading capacity, controllable drug release, rapid and smart responses to stimuli and versatile functionalities. In this study, we have made a systematic review of all aspects of nano-vesicles as drug delivery vectors for cancer treatment, mainly including the following aspect: characteristics of polymeric nanovesicles, polymeric nanovesicle synthesis, and recent progress in applying polymeric nanovesicles in antitumor drug delivery. Polymer nanovesicles have the advantages of synergistic photothermal and imaging in improving the anticancer effect. Therefore, we believe that drug carrier of polymer nanovesicles is a key direction for cancer treatment.
    Keywords:  anticancer drug; cancer therapy; drug delivery; nanovesicle; polymeric nanovesicles
    DOI:  https://doi.org/10.3389/fbioe.2022.850366
  14. Curr Top Med Chem. 2022 Mar 03.
    Look into my onco-forest - review of plant natural products with anticancer activity.
    Izabela Michalak, Mirosława Püsküllüoğlub.
      Cancer is a multistage process that can be treated by numerous modalities including systemic treatment. About half of the molecules that have been approved in the last few decades count for plant derivatives. This review presents the application of tree/shrub-derived biologically active compounds as anticancer agents. Different parts of trees/shrubs - wood, bark, branches, roots, leaves, needles, fruits, flowers etc. - contain a wide variety of primary and secondary metabolites, which demonstrate anticancer properties. Special attention was paid to phenolics (phenolic acids and polyphenols, including flavonoids and non-flavonoids (tannins, lignans, stilbenes)), essential oils and their main constituents such as terpenes/terpenoids, phytosterols, alkaloids and many others. Anticancer properties of these compounds are mainly attributed to their strong antioxidant properties. In vitro experiments on various cancer cell lines revealed a cytotoxic effect of tree-derived extracts. Mechanisms of anticancer action of the extracts are also listed. Examples of drugs that successfully underwent clinical trials with well-established position in the guidelines created by oncological societies are provided. The review also focuses on directions for the future in the development of anticancer agents derived from trees/shrubs. Applying biologically active compounds derived from trees and shrubs as anticancer agents continuously seems a promising strategy in cancer systemic treatment.
    Keywords:  Anticancer drugs; Biologically active compounds; Cytotoxicity.; Extraction; Shrub; Tree
    DOI:  https://doi.org/10.2174/1568026622666220303112218
  15. Cytokine Growth Factor Rev. 2022 Jan 21. pii: S1359-6101(22)00006-5. [Epub ahead of print]
    Crosstalk between ferroptosis and the epithelial-mesenchymal transition: Implications for inflammation and cancer therapy.
    Nasim Ebrahimi, Samaneh Adelian, Siavash Shakerian, Maral Afshinpour, Siavash Rahimian Chaleshtori, Nadi Rostami, Fatemeh Rezaei-Tazangi, Sheida Beiranvand, Michael R Hamblin, Amir Reza Aref.
      Both genomic instability and the presence of chronic inflammation are involved in carcinogenesis and tumor progression. These alterations predispose the cancer cells to undergo metabolic reprogramming as well as the epithelial-mesenchymal transition (EMT). These pathways allow cancer cells to avoid apoptosis and stimulate tumor progression. EMT is an important early event in tumor cell invasion, which can be regulated through inflammatory signaling pathways. Cancer cells undergoing EMT are vulnerable to cell death by the process of ferroptosis. Ferroptosis is a form of regulated cell death involving iron-dependent lipid peroxidation, designed to maintain cellular homeostasis. Several reports have linked ferroptosis, inflammation, and cancer. Ferroptosis inhibitors and EMT inducers have been used to understand the anti-inflammatory and anticancer effects in experimental models. A better understanding of the crosstalk between ferroptosis and EMT, and the involvment of inflammatory mediators may accelerate the discovery of therapeutic strategies to eradicate cancer cells and overcome drug-resistance.
    Keywords:  Cancer cells; Cancer therapy; EMT; Ferroptosis; Inflammation
    DOI:  https://doi.org/10.1016/j.cytogfr.2022.01.006
  16. Biomed Pharmacother. 2022 Feb 28. pii: S0753-3322(22)00135-4. [Epub ahead of print]148 112747
    Ferroptosis in hematological malignancies and its potential network with abnormal tumor metabolism.
    Jiasi Zhang, Yuxi Liu, Qun Li, Aoshuang Xu, Yu Hu, Chunyan Sun.
      Ferroptosis, a new type of regulated cell death, displays characteristics that transparently differ from apoptosis, autophagy and necroptosis. There is growing appreciation that targeting ferroptosis is potentially a novel strategy in anti-tumor therapy, especially for invasive malignancies demonstrating resistance to chemotherapy. Almost all types of cancer cells depend on abnormal metabolic activities to participate in vicious progression, giving the possibility to interfere with underlying metabolic preferences and compromise malignant cells by inducing ferroptosis. In this perspective, we give an overview of potential interactions between ferroptosis and abnormal tumor metabolism, with special focus on systematic researches in hematological malignancies.
    Keywords:  Ferroptosis; Hematological cancer; Tumor metabolism
    DOI:  https://doi.org/10.1016/j.biopha.2022.112747
  17. Biosci Rep. 2022 Mar 03. pii: BSR20212171. [Epub ahead of print]
    Targeting ASCT2-mediated Glutamine Metabolism Inhibits Proliferation and Promotes Apoptosis of Pancreatic Cancer cell.
    Wenbin Wang, Haihua Pan, Feihua Ren, Hongxia Chen, Ping Ren.
      Some tumor cells have a high rate of glutamine uptake and exhibit glutamine addiction. Alanine serine cysteine‑preferring transporter 2 (ASCT2) is a major mediator of glutamine supply in many tumor cells, but the underlying effects and mechanisms of ASCT2 in pancreatic cancer are largely unknown. Our results show that ASCT2 expression is significantly higher in pancreatic cancer than in normal pancreatic duct cells and pancreas. Utilizing the Kaplan-Meier Plotter Database, a high expression of SLC1A5 mRNA was significantly associated with poor overall survival in patients with pancreatic cancer. ShRNA-mediated inhibition of ASCT2 function in vitro can significantly decrease glutamine consumption, α-ketoglutarate production and ATP generation and increase the reactive oxygen species level. Moreover, the antioxidant N-acetylcysteine partially attenuated the increase in the reactive oxygen species levels and reduced ATP generation. These data suggest that ASCT2 mediates glutamine metabolism and maintains redox homeostasis in pancreatic cancer. To further investigate whether ASCT2 is involved in pancreatic cancer cell growth, we blocked ASCT2 activity with the ASCT2 inhibitor L-γ-glutamyl-p-nitroanilide and silenced the expression of ASCT2 with specific shRNAs. We found that the growth of pancreatic cancer cells was significantly inhibited. Additionally, knockdown of ASCT2 induced apoptosis through the Akt/mTOR signaling pathway. Furthermore, the loss of ASCT2 in BxPC3 cell xenografts significantly inhibited tumor growth in vivo, and this effect was associated with an increase in cleaved caspase-3 expression and a decrease in Ki67 staining. Taken together, our results show that ASCT2 may be utilized as a putative therapeutic target for pancreatic cancer.
    Keywords:  ASCT2; apoptosis; glutamine metabolism; pancreatic cancer
    DOI:  https://doi.org/10.1042/BSR20212171
  18. Nov Approaches Cancer Study. 2021 ;6(3): 609-614
    Dendrimer-Based Nanomedicine (Paramagnetic Nanoparticle, Nanocombretastatin, Nanocurcumin) for Glioblastoma Multiforme Imaging and Therapy.
    Stephen L Brown, James M Snyder, Meser M Ali.
      In brain tumors, delivering nanoparticles across the blood-brain tumor barrier presents a major challenge. Dual mode magnetic resonance imaging and fluorescent imaging probes have been developed where relaxation based Gd-DOTA or ParaCEST agents and a Near-Infrared (NIR) fluorescent dye, DL680 were conjugated on the surface of dendrimer. The in vivo and ex vivo imaging of the dual-modality contrast agent showed excellent potential utility for identifying the location of glioma tumors. Systemic delivery of the subsequent nano-sized agent demonstrated glioma-specific accumulation, probably due to the enhanced permeability and retention effect. The biodistribution studies revealed the G5 agents have accumulated in the glioma tumor and the liver while a G3 agent only accumulated in the brain tumor but not in the liver or kidney. Hydrophobic drug molecules like Combrestatin A4 (CA4) or curcumin have also been conjugated with dendrimers that provided high aqueous solubility with improved therapeutic effect.
    Keywords:  Cancer imaging and therapy; Dendrimer; Glioma; Nanomedicine
    DOI:  https://doi.org/10.31031/nacs.2021.06.000639
  19. Biochem J. 2022 Mar 18. 479(5): 583-607
    Insulin and cancer: a tangled web.
    Brooks P Leitner, Stephan Siebel, Ngozi D Akingbesote, Xinyi Zhang, Rachel J Perry.
      For a century, since the pioneering work of Otto Warburg, the interwoven relationship between metabolism and cancer has been appreciated. More recently, with obesity rates rising in the U.S. and worldwide, epidemiologic evidence has supported a link between obesity and cancer. A substantial body of work seeks to mechanistically unpack the association between obesity, altered metabolism, and cancer. Without question, these relationships are multifactorial and cannot be distilled to a single obesity- and metabolism-altering hormone, substrate, or factor. However, it is important to understand the hormone-specific associations between metabolism and cancer. Here, we review the links between obesity, metabolic dysregulation, insulin, and cancer, with an emphasis on current investigational metabolic adjuncts to standard-of-care cancer treatment.
    Keywords:  cancer metabolism; diabetes; immunometabolism
    DOI:  https://doi.org/10.1042/BCJ20210134
  20. J Ethnopharmacol. 2022 Feb 25. pii: S0378-8741(22)00182-9. [Epub ahead of print] 115144
    Journey of Alpinia galanga from kitchen spice to nutraceutical to folk medicine to nanomedicine.
    Arya Kadukkattil Ramanunny, Sheetu Wadhwa, Monica Gulati, Sukriti Vishwas, Rubiya Khursheed, Keshav Raj Paudel, Saurabh Gupta, Omji Porwal, Saad M Alshahrani, Niraj Kumar Jha, Dinesh Kumar Chellappan, Parteek Prasher, Gaurav Gupta, Jon Adams, Kamal Dua, Devesh Tewary, Sachin Kumar Singh.
       ETHANOPHARMACOLOGICAL IMPORTANCE: Alpinia galanga (L.) Willd, belonging to Zingiberaceae family is used as a spice and condiment in various culinary preparations of Indonesia, Thailand and Malaysia.It has been also used as a key ingredient in various traditional systems of medicine for the treatment of throat infection, asthma, urinary ailments, inflammation and rheumatism amongst other conditions. A. galanga (AG) is widely used as a functional food and included in various preparations to obtain its nutraceutical and pharmacological benefits of its phytoconstituents such as phenyl propanoids, flavonoids and terpenoids. Over the past decades, several researchers have carried out systematic investigation on various parts of AG. Numerous studies on AG rhizomes have shown positive pharmacological effects such as anti-inflammatory, anticancer, antipsoriasis, antiallergic, neuroprotective and thermogenesis. Till date, no comprehensive review summarizing the exploitation of AG into nanomedicine has been published.
    AIM OF THE REVIEW: This comprehensive review aims to briefly discuss cultivation methods, propagation techniques, extraction processes for AG. The ethnopharmacological uses and pharmacological activities of AG extracts and its isolates are discussed in detail which may contribute well in further development of novel drug delivery system (NDDS) i.e. future nanomedicine.
    MATERIALS AND METHODS: Information about AG was collected using search engine tools such as Google, Google Scholar, PubMed, Google Patent, Web of Science and bibliographic databases of previously published peer-reviewed review articles and research works were explored. The obtained data sets were sequentially arranged for better understanding of AG's potential.
    RESULTS: More advanced genetic engineering techniques have been utilized in cultivation and propagation of AG for obtaining better yield. Extraction, isolation and characterization techniques have reported numerous phytoconstituents which are chemically phenolic compounds (phenyl propanoids, flavonoids, chalcones, lignans) and terpenes. Ethnopharmacological uses and pharmacological activity of AG are explored in numerous ailments, their mechanism of action and its further potential to explore into novel drug delivery system are also highlighted.
    CONCLUSIONS: The review highlights the importance of plant tissue culture in increasing the production of AG plantlets and rhizomes. It was understood from the review that AG and its phytoconstituents possess numerous pharmacological activities and have been explored for the treatment of cancer, microbial infection, gastrointestinal disorders, neuroprotective effects, obesity and skin disorders. However, the use of AG as alternative medicine is limited owing to poor solubility of its bioactive components and their instability. To overcome these challenges, NDDS have been utilized and found good success in overcoming its aforementioned challenges. Furthermore, efforts are required towards development of scalable, non-toxic and stable NDDS of AG and/or its bioactives.
    Keywords:  Alpinia galanga; Extraction; Micropropagation; Nanomedicine; Nutraceutical
    DOI:  https://doi.org/10.1016/j.jep.2022.115144
  21. Expert Opin Drug Discov. 2022 Mar 04. 1-17
    Frankincense diterpenes as a bio-source for drug discovery.
    Hidayat Hussain, Luay Rashan, Uzma Hassan, Muzaffar Abbas, Faruck L Hakkim, Ivan R Green.
       INTRODUCTION: Frankincense (Boswellia sp.) gum resins have been employed as an incense in cultural and religious ceremonies for many years. Frankincense resin has over the years been employed to treat depression, inflammation, and cancer in traditional medicines.
    AREAS COVERED: This inclusive review focuses on the significance of frankincense diterpenoids, and in particular, incensole derivatives for establishment future treatments of depression, neurological disorders, and cancer. The authors survey the available literature and furnish an overview of future perspectives of these intriguing molecules.
    EXPERT OPINION: Numerous diterpenoids including cembrane, prenylaromadendrane, and the verticillane-type have been isolated from various Boswellia resins. Cembrane-type diterpenoids occupy a crucial position in pharmaceutical chemistry and related industries because of their intriguing biological and encouraging pharmacological potentials. Several cembranes have been reported to possess anti-Alzheimer, anti-inflammatory, hepatoprotective, and antimalarial effects along with a good possibility to treat anxiety and depression. Although some slight drawbacks of these compounds have been noted, including the selectivity of these diterpenoids, there is a great need to address these in future research endeavors. Moreover, it is vitally important for medicinal chemists to prepare libraries of incensole-heterocyclic analogs as well as hybrid compounds between incensole or its acetate and anti-depressant or anti-inflammatory drugs.
    Keywords:  Frankincense; alzheimer’s; cembrane; depression; inflammation; prenylaromadendrane; verticillane
    DOI:  https://doi.org/10.1080/17460441.2022.2044782
  22. Front Bioeng Biotechnol. 2022 ;10 840395
    Microneedle-Mediated Transdermal Delivery of Drug-Carrying Nanoparticles.
    Xue Jiang, Huanhuan Zhao, Wei Li.
      Drug-carrying nanoparticles have obtained great attention for disease treatments due to the fact that they can improve drug solubility, provide drug protection and prolong release duration, thus enhancing drug bioavailability and increasing therapeutic efficacy. Although nanoparticles containing drugs can be administered via different routes such as oral, intravenous and ocular, transdermal delivery of nanoparticles mediated by microneedles has attracted considerable interest due to the capability of circumventing enzymatic degradation caused by gastrointestinal track, and increasing patient compliance by reducing pain associated with hypodermic injection. In this review, we first introduce four types of nanoparticles that were used for drug delivery, and then summarize strategies that have been employed to facilitate delivery of drug-loaded nanoparticles via microneedles. Finally, we give a conclusion and provide our perspectives on the potential clinical translation of microneedle-facilitated nanoparticles delivery.
    Keywords:  controlled release; drug delivery; microneedle; nanoparticles; transdermal delivery
    DOI:  https://doi.org/10.3389/fbioe.2022.840395
  23. Food Res Int. 2022 Mar;pii: S0963-9969(21)00829-2. [Epub ahead of print]153 110929
    Flavonoids, anthocyanins, betalains, curcumin, and carotenoids: Sources, classification and enhanced stabilization by encapsulation and adsorption.
    Betina Luiza Koop, Milena Nascimento da Silva, Fabíola Diniz da Silva, Kennya Thayres Dos Santos Lima, Lenilton Santos Soares, Cristiano José de Andrade, Germán Ayala Valencia, Alcilene Rodrigues Monteiro.
      Bioactive compounds have remarkable biological activities for health, nutrition, and food preservation. However, these compounds are chemically unstable maily when exposure at high temperatures, light, and humidity. Several stabilization techniques have been used to protect these compounds, expanding their application range. Therefore, this review aims to show the main bioactive compounds currently studied and the use of stabilization techniques, such as encapsulation and adsorption, for food application. A broader systematic classification of bioactive compounds based on phenolic and non-phenolic sub-levels was suggested, which can assist in a deeper discussion of results, including the correlation of biological activities, their synergistic effects, and their enhanced stabilization on materials that promote a well-controlled delivery (higher bioavailability). Research on Scopus Database was used to identify the scientific trends for stabilization methods (2016-2020). This review article focused on analyzing bioactive encapsulation using cold processing techniques such as ionic gelation, emulsification, complex coacervation, and adsorption to expand production and application in the food sector.
    Keywords:  Food by-products; Functional food; Nanovehicle-based delivery systems; Natural additives; Natural dyes; Nutraceuticals; Phytochemicals; Polyphenols
    DOI:  https://doi.org/10.1016/j.foodres.2021.110929
  24. ACS Biomater Sci Eng. 2022 Mar 04.
    Fabrication of Laponite-Reinforced Dextran-Based Hydrogels for NIR-Responsive Controlled Drug Release.
    Jinwei Luo, Zewei Ma, Fengjuan Yang, Tianhua Wu, Shengwu Wen, Jingxian Zhang, Langhuan Huang, Suiping Deng, Shaozao Tan.
      Natural polymer gels with sensitivity to near-infrared (NIR) light have attracted the attention of scientists working on intelligent drug delivery systems. Compared to ultraviolet or visible light, NIR light has the advantages of strong trigger levels, deep penetration through affected tissues, and fewer side effects. Herein, we present a topical photothermal hydrogel for NIR-controlled drug delivery. The proposed DexIEM-GM-Laponite hydrogel was prepared through free radical polymerization of vinyl-functionalized dextran (DexIEM), vinyl-modified graphene oxide (GM), and Laponite; thereafter, the hydrogel was loaded with ciprofloxacin (CIP, an antibacterial drug) as a model drug. With the Laponite content increased, the density of crosslinking in the hydrogel increased, and its mechanical properties improved noticeably. Under NIR irradiation, the DexIEM-GM-Laponite hydrogel exhibited a photothermal property, where the surface temperature increased from 26.8 to 55.5 °C. The simulation of subcutaneous drug delivery experiments ex vivo showed that under the specified pork tissue thickness (2, 4, and 6 mm), the CIP release remained NIR-controllable. Additionally, the results of the antibacterial performance tests indicated the excellent antibacterial effect of the hydrogel, and the blood hemolysis ratio of the hydrogel was less than 5%, signifying good blood compatibility. This work will provide an avenue for the application of NIR light-responsive materials in antimicrobial therapy.
    Keywords:  antibacterial; drug delivery; drug-loaded hydrogel; near-infrared radiation; photothermal
    DOI:  https://doi.org/10.1021/acsbiomaterials.1c01389
  25. Int J Biol Macromol. 2022 Feb 28. pii: S0141-8130(22)00377-4. [Epub ahead of print]
    pH-sensitive hyaluronic acid-targeted prodrug micelles constructed via a one-step reaction for enhanced chemotherapy.
    Min Li, Ling'e Zhang, Yang Xuan, Defu Zhi, Wei Wang, Wenjun Zhang, Yinan Zhao, Shufen Zhang, Shubiao Zhang.
      Although many chemotherapy prodrugs have been developed for tumor therapy, non-targeted delivery, uncontrolled release and tedious construction procedure of prodrugs still limit their clinical application in tumor treatment. In this work, hyaluronic acid (HA) which has tumor-targeting ability was used to conjugate to antitumor drug podophyllotoxin (PPT) to construct a pH-sensitive prodrug named HA-CO-O-PPT just via a one-step esterification reaction. The HA-CO-O-PPT spontaneously assembled into nano spherical micelles in aqueous medium, which had outstanding serum stability and blood compatibility. The obtained prodrug micelles (named HP micelles) exhibited a pH-responsive drug release mode with cumulative release reaching 81.2% due to their dissociation in response to acid stimulus, and had a high cellular uptake efficiency beyond 97% owing to HA receptor-mediated targeting. Furthermore, it was found that the prodrug micelles showed excellent antitumor activities in vivo with the tumor inhibition ratio up to 85% and negligible systemic toxicity. Accordingly, the pH-responsive HP micelles constructed by a simple one-step reaction, could be a promising candidate as a chemotherapeutic agent for cancer therapy.
    Keywords:  Hyaluronic acid; Podophyllotoxin; Prodrug micelles; Tumor-targeted drug delivery; pH-responsive
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.02.131
  26. Phytother Res. 2022 Mar 04.
    Protective effects of functional foods against Parkinson's disease: A narrative review on pharmacology, phytochemistry, and molecular mechanisms.
    Milad Iranshahy, Behjat Javadi, Amirhossein Sahebkar.
      In Persian Medicine (PM), PD (brain-based tremor) is a known CNS disorder with several therapeutic and preventive options. In their medical textbooks and pharmacopeias, Persian great scientists such as Rhazes (854-925 AD), Avicenna (980-1037 AD), and Jorjani (1042-1136 AD), have discussed pharmacological and nutritional strategies for the prevention, slowing progression, and treatment of PD. In the present study, we surveyed plant- and animal-based foods recommended by PM for the prevention and treatment of CNS-related tremors. In vivo and in-vitro pharmacological evidence supporting the beneficial effects of PM-recommended foods in prevention and alleviating PD, major active phytochemicals along with the relevant mechanisms of action were studied. Several PM plants possess potent antioxidant, antiinflammatory, and PD preventing properties. Garlic and allicin, cabbage and isothiocyanates, chickpea seed and its O-methylated isoflavones biochanin A and formononetin, cinnamon, and cinnamaldehyde, saffron and its crocin, crocetin, and safranal, black cumin and its thymoquinone, black pepper and piperine, pistachio and genistein and daidzein, and resveratrol are among the most effective dietary itemsagainst PD. They act through attenuating neurotoxin-induced memory loss and behavioral impairment, oxidative stress, and dopaminergic cell death. PM-recommended foods can help alleviate PD progression and also discovering and developing new neuroprotective anti-PD pharmaceuticals.
    Keywords:  Parkinson's disease; Persian medicine; diet; neurodegeneration; neuropharmacology
    DOI:  https://doi.org/10.1002/ptr.7425
  27. ACS Appl Bio Mater. 2022 Feb 28.
    Recent Progress in Nanostructured Smart Drug Delivery Systems for Cancer Therapy: A Review.
    Md Ishak Khan, M Imran Hossain, M Khalid Hossain, M H K Rubel, K M Hossain, A M U B Mahfuz, Muzahidul I Anik.
      Traditional treatment approaches for cancer involve intravenous chemotherapy or other forms of drug delivery. These therapeutic measures suffer from several limitations such as nonspecific targeting, poor biodistribution, and buildup of drug resistances. However, significant technological advancements have been made in terms of superior modes of drug delivery over the last few decades. Technical capability in analyzing the molecular mechanisms of tumor biology, nanotechnology─particularly the development of biocompatible nanoparticles, surface modification techniques, microelectronics, and material sciences─has increased. As a result, a significant number of nanostructured carriers that can deliver drugs to specific cancerous sites with high efficiency have been developed. This particular maneuver that enables the introduction of a therapeutic nanostructured substance in the body by controlling the rate, time, and place is defined as the nanostructured drug delivery system (NDDS). Because of their versatility and ability to incorporate features such as specific targeting, water solubility, stability, biocompatibility, degradability, and ability to reverse drug resistance, they have attracted the interest of the scientific community, in general, and nanotechnologists as well as biomedical scientists. To keep pace with the rapid advancement of nanotechnology, specific technical aspects of the recent NDDSs and their prospects need to be reported coherently. To address these ongoing issues, this review article provides an overview of different NDDSs such as lipids, polymers, and inorganic nanoparticles. In addition, this review also reports the challenges of current NDDSs and points out the prospective research directions of these nanocarriers. From our focused review, we conclude that still now the most advanced and potent field of application for NDDSs is lipid-based, while other significantly potential fields include polymer-based and inorganic NDDSs. However, despite the promises, challenges remain in practical implementations of such NDDSs in terms of dosage and stability, and caution should be exercised regarding biocompatibility of materials. Considering these aspects objectively, this review on NDDSs will be particularly of interest for small-to-large scale industrial researchers and academicians with expertise in drug delivery, cancer research, and nanotechnology.
    Keywords:  biocompatibility; cancer therapy; cytotoxicity evaluation; nanoparticles; nanotechnology; smart drug delivery
    DOI:  https://doi.org/10.1021/acsabm.2c00002
  28. J Nanobiotechnology. 2022 Mar 04. 20(1): 106
    Multifunctional photodynamic/photothermal nano-agents for the treatment of oral leukoplakia.
    Lin Lin, Chuanhui Song, Zheng Wei, Huihui Zou, Shengwei Han, Zichen Cao, Xinyu Zhang, Guorong Zhang, Jianchuan Ran, Yu Cai, Wei Han.
      Oral leukoplakia (OLK) has gained extensive attention because of the potential risk for malignant transformation. Photosensitizers (PSs) played an indispensable role in the photodynamic therapy (PDT) of OLK, but the poor light sensitivity greatly hampered its clinical application. Herein, a novel organic photosensitive ITIC-Th nanoparticles (ITIC-Th NPs) were developed for OLK photodynamic/photothermal therapy (PTT). ITIC-Th NPs present both high photothermal conversion efficiency (~ 38%) and suitable reactive oxygen species (ROS) generation ability under 660 nm laser irradiation, making them possess excellent PDT and PTT capability. In 4-nitroquinoline 1-oxide (4NQO)-induced oral precancerous animal models, ITIC-Th NPs effectively suppress the OLK's cancerization without apparent topical or systemic toxicity in vivo. This study offers a promising therapeutic strategy for PDT and PTT in OLK treatment, and this study is the first interdisciplinary research in the field of multimodal therapy for OLK.
    Keywords:  Nanomedicine; Oral leukoplakia; Photodynamic therapy; Tumor
    DOI:  https://doi.org/10.1186/s12951-022-01310-2
  29. Chin J Physiol. 2022 Jan-Feb;65(1):65(1): 12-20
    Current research status of alkaloids against breast cancer.
    Zhiqiang Hu, Jingling Pan, Jialing Wang, Yanmin Pei, Ru Zhou.
      Breast cancer is one of the most common malignant tumors in women worldwide. Surgery, chemotherapy, and targeted drugs are the main methods currently used in clinical treatment of breast cancer. Although they can improve the symptoms of patients, they are also accompanied by a large number of side effects. Because of its multiple targets, traditional Chinese medicine can improve the quality of life of breast cancer patients and reduce the side effects associated with chemotherapy, which plays an important role in the treatment of breast cancer. To a certain extent, traditional Chinese medicine has advantages that modern medicine does not have in the treatment of breast cancer. Alkaloids are active ingredients widely distributed in traditional Chinese medicine, which have a variety of pharmacological effects including anti-inflammatory, analgesic, and antitumor effects. The author reviewed the literature on the treatment of breast cancer with alkaloids extracted from traditional Chinese medicine in recent years, and discussed the unique advantages of alkaloids in the treatment of breast cancer.
    Keywords:  Alkaloid; Chinese medicine; breast cancer; mechanism; treatment
    DOI:  https://doi.org/10.4103/cjp.cjp_89_21
  30. Front Pharmacol. 2021 ;12 825330
    Progress in the Mechanism of Autophagy and Traditional Chinese Medicine Herb Involved in Dementia.
    Pengyu Tao, Jing Ji, Simeng Gu, Qian Wang, Yuzhen Xu.
      Dementias is a kind of neurodegenerative disease, which occurs among the aging population. Current therapeutic outcome for dementia is limited. The medical use of herbal plant has a rich history in traditional Chinese medicine practice for thousands of years. Herbal medicine (HM) may provide a positive effect for prevention and treatment in dementia. As an alternative treatment to dementia, there has been a growing interest in HM extracts in scientific community as a result of its promising study results, mainly in animal experiment. At the molecular level, HM extracts trigger autophagy and reduce generation of reactive oxygen species (ROS) while inhibiting inflammation and reduce neurotoxicity. Experiments both in vivo and in vitro have identified certain potential of HM extracts and natural products as an important regulator factor in mediating autophagy, which might contribute to the improvement of dementia. This brief review not only summarizes the mechanism of autophagy in dementia but also offers a general understanding of the therapeutic mechanism of HM extracts in treating dementia and evaluates the potential clinical practice of HM in general.
    Keywords:  Chinese herbal medicine extracts; apoptosis; autophagy; dementia; inflammation; oxidative stress
    DOI:  https://doi.org/10.3389/fphar.2021.825330
  31. Mol Metab. 2022 Feb 24. pii: S2212-8778(22)00035-7. [Epub ahead of print] 101466
    Reprogramming hormone sensitive prostate cancer to a lethal neuroendocrine cancer lineage by mitochondrial pyruvate carrier (MPC).
    Huan Xu, Zhixiao Liu, Dajun Gao, Peizhang Li, Yanting Shen, Yi Sun, Lingfan Xu, Nan Song, Yue Wang, Ming Zhan, Xu Gao, Zhong Wang.
      Cell lineage reprogramming is the main way for cancer cells to acquire drug resistance and escape targeted therapy. The use of potent targeted therapies in cancers has led to the development of highly aggressive carcinoma, including neuroendocrine prostate cancer (NEPC). Although metabolic reprogramming has been reported to be essential for tumor growth and energy production, the relationship between metabolic reprogramming and lineage differentiation which can cause the hormone therapy resistance has never been reported in prostate cancer (PCa). Moreover, as there is still no efficient therapy for NEPC, it is urgent to reverse this lineage differentiation during the hormone therapy. Here for the first time, we used in vitro and in vivo human PCa models to study the effect of metabolic reprogramming on the lineage differentiation from androgen receptor (AR)-dependent adenocarcinoma to AR-independent NEPC. This lineage differentiation leads to the antiandrogen drug resistance and tumor development. This phenotype is enabled by the loss of mitochondrial pyruvate carrier (MPC), the gate for mitochondrial pyruvate influx, and can be reversed by MPC overexpression. Morphologic and cellular studies also demonstrate the M2-pyruvate kinase (PKM2) involved epithelium-mesenchymal transition process mediated this lineage alteration. Its inhibition is a potential treatment for MPC-lo tumors. All of these results suggest that metabolic rewiring can act as a starter for increased cellular plasticity which leads to antiandrogen therapy resistance through lineage differentiation. This study provides us a potent treatment target for therapy induced, enzalutamide resistant NE like prostate cancer.
    Keywords:  castration-resistant prostate cancer; metabolic reprogramming; mitochondrial pyruvate carrier; neuroendocrine prostate cancer
    DOI:  https://doi.org/10.1016/j.molmet.2022.101466
  32. Signal Transduct Target Ther. 2022 02 28. 7(1): 64
    Asymmetric, amphiphilic RGD conjugated phthalocyanine for targeted photodynamic therapy of triple negative breast cancer.
    Rui Li, Yiming Zhou, Yijia Liu, Xingpeng Jiang, Wenlong Zeng, Zhuoran Gong, Gang Zheng, Desheng Sun, Zhifei Dai.
      Targeted photodynamic therapy (TPDT) is considered superior to conventional photodynamic therapy due to the enhanced uptake of photosensitizers by tumor cells. In this paper, an amphiphilic and asymmetric cyclo-Arg-Gly-Asp-d-Tyr-Lys(cRGDyK)-conjugated silicon phthalocyanine (RSP) was synthesized by covalently attaching the tripeptide Arg-Gly-Asp (RGD) to silicone phthalocyanine in the axial direction for TPDT of triple-negative breast cancer (TNBC). RSP was characterized by spectroscopy as a monomer in physiological buffer. Meanwhile, the modification of RSP with RGD led to a high accumulation of the photosensitizer in TNBC cells overexpressing ανβ3 integrin receptors which can bind RGD, greatly reducing the risk of phototoxicity. In vitro photodynamic experiments showed that the IC50 of RSP was 295.96 nM in the 4T1 cell line, which caused significant apoptosis of the tumor cells. The tumor inhibition rate of RSP on the orthotopic murine TNBC achieved 74%, while the untargeted photosensitizer exhibited no obvious tumor inhibition. Overall, such novel targeted silicon phthalocyanine has good potential for clinical translation due to its simple synthesis route, strong targeting, and high therapeutic efficacy for TPDT treatment of TNBC.
    DOI:  https://doi.org/10.1038/s41392-022-00906-2
  33. JOM (1989). 2022 Feb 24. 1-16
    A Review on Curcumin-Loaded Electrospun Nanofibers and their Application in Modern Medicine.
    Souradeep Mitra, Tarun Mateti, Seeram Ramakrishna, Anindita Laha.
      Herbal drugs are safe and show significantly fewer side effects than their synthetic counterparts. Curcumin (an active ingredient primarily found in turmeric) shows therapeutic properties, but its commercial use as a medication is unrealized, because of doubts about its potency. The literature reveals that electrospun nanofibers show simplicity, efficiency, cost, and reproducibility compared to other fabricating techniques. Forcespinning is a new technique that minimizes limitations and provides additional advantages to electrospinning. Polymer-based nanofibers-whose advantages lie in stability, solubility, and drug storage-overcome problems related to drug delivery, like instability and hydrophobicity. Curcumin-loaded polymer nanofibers show potency in healing diabetic wounds in vitro and in vivo. The release profiles, cell viability, and proliferation assays substantiate their efficacy in bone tissue repair and drug delivery against lung, breast, colorectal, squamous, glioma, and endometrial cancer cells. This review mainly discusses how polymer nanofibers interact with curcumin and its medical efficacy.
    DOI:  https://doi.org/10.1007/s11837-022-05180-9
  34. ACS Appl Bio Mater. 2022 Mar 03.
    Ultrasound versus Light: Exploring Photophysicochemical and Sonochemical Properties of Phthalocyanine-Based Therapeutics, Theoretical Study, and In Vitro Evaluations.
    Emre Güzel, Göknur Yaşa Atmaca, Aleksey E Kuznetsov, Aysegul Turkkol, Mehmet Dincer Bilgin, Ali Erdoğmuş.
      Photodynamic therapy (PDT) applications carried out with the assistance of ultrasound have attracted significant attention in recent years. The use of phthalocyanines, which are an important component as photosensitizers in PDT, is becoming more important day by day. In therapeutic applications, phthalocyanines can promote the production of reactive oxygen species. Motivated by this fact, the syntheses of metal-free (2), gallium (3), and indium (4) phthalocyanines have been achieved by substituting 4-(cinnamyloxy)phthalonitrile for the first time to evaluate their therapeutic applications. Additionally, photophysicochemical, sonophotochemical, and in vitro evaluations of phthalocyanines have been reported. To the best of our knowledge, this is the first study of the use of phthalocyanines with different metal ions as potential photosensitizers for sonophotodynamic therapy (SPDT) applications in gastric cancer cell lines. The results show that the quantum yield of the generation of singlet oxygen increased in sonophotochemical studies (ΦΔ = 0.55 (2), 0.85 (3), 0.96 (4)), compared to photochemical studies (ΦΔ = 0.22 (2), 0.61 (3), 0.78 (4)). The density functional theory (DFT) results are in good agreement with the experimental results and suggest increased reactivity of phthalocyanines 3 and 4 in various redox processes, thus implying their applicability and usefulness as potential therapeutic agents. These phthalocyanines are effective sensitizers for PDT, sonodynamic therapy (SDT), and SPDT against MKN-28 gastric cancer cell line in vitro. All three treatments decreased cell viability and induced apoptosis in the gastric cancer cell line. However, indium phthalocyanine (4)-mediated SPDT was a more effective treatment modality compared to indium phthalocyanine (4)-mediated PDT and SDT. Also, indium phthalocyanine (4) was found to be a more effective sensitizer to activate apoptosis compared to the other phthalocyanines. To sum up, phthalocyanine-mediated SPDT enhances the cytotoxic effect on gastric cancer cells more than the effect of SDT or PDT alone.
    Keywords:  photodynamic therapy; phthalocyanine; sensitizer; sonodynamic therapy; therapeutics; time-dependent DFT
    DOI:  https://doi.org/10.1021/acsabm.1c01199
  35. Drug Deliv. 2022 Dec;29(1): 714-727
    Development and optimization of curcumin analog nano-bilosomes using 21.31 full factorial design for anti-tumor profiles improvement in human hepatocellular carcinoma: in-vitro evaluation, in-vivo safety assay.
    Haidy Abbas, Yasmin A El-Feky, Majid Mohammad Al-Sawahli, Nehal M El-Deeb, Hala Bakr El-Nassan, Mariam Zewail.
      Curcumin (CU) is a natural polyphenolic phytoingredient. CU has anti-inflammatory, anti-oxidant, and anticancer activities. The poor solubility, bioavailability, and stability of CU diminish its clinical application. Hence, structural modification of CU is highly recommended. The CU analog; 3,5-bis(4-bromobenzylidene)-1-propanoylpiperidin-4-one (PIP) exhibited high stability, safety, and more potent antiproliferative activity against hepatocellular carcinoma. In the present study, nano-bilosomes (BLs) were formulated to augment PIP delivery and enhance its solubility. A 21.31 full factorial design was adopted to prepare the synthesized PIP-loaded BLs. Optimized F4 showed a biphasic release pattern extended over 24 h, with EE%, ZP, and PS of 90.21 ± 1.0%, -27.05 ± 1.08 mV, and 111.68 ± 1.4 nm. PIP-loaded BLs were tested for safety against a non-cancerous cell line (Wi-38) and for anticancer activity against the Huh-7 human hepatocellular carcinoma cells and compared to the standard anticancer drug doxorubicin (Dox). The anticancer selectivity index of PIP-loaded BLs recorded 420.55 against Huh-7 liver cancer cells, markedly higher than a CU suspension (18.959) or the Dox (20.82). The antiproliferative activity of nano-encapsulated PIP was roughly equivalent to Dox. PIP-loaded BLs, showed enhanced drug solubility, and enhanced anticancer effect, with lower toxicity and higher selectivity against Huh-7 liver cancer cells, compared to the parent CU.
    Keywords:  3,5-bis(4-bromobenzylidene)-1-propanoylpiperidin-4-one; Curcumin; bile salts; hepatocellular carcinoma; nano-bilosomes
    DOI:  https://doi.org/10.1080/10717544.2022.2044938
  36. Front Bioeng Biotechnol. 2021 ;9 811917
    Nanomedicine of Plant Origin for the Treatment of Metabolic Disorders.
    Fang Hu, Dong-Sheng Sun, Kai-Li Wang, Dan-Ying Shang.
      Metabolic disorders are major clinical challenges of health that are progressing globally. A concurrence of metabolic disorders such as obesity, insulin resistance, atherogenic dyslipidemia, and systematic hypertension leads to metabolic syndrome. Over the past years, the metabolic syndrome leads to a five- and two-fold rise in diabetes mellitus type II and cardiovascular diseases. Natural products specifically plant extracts have insulin-sensitizing, anti-inflammatory, and antioxidant properties and are also considered as an alternative option due to few adverse effects. Nanotechnology is one of the promising strategies, which improves the effectiveness of treatment and limits side effects. This review mainly focuses on plant extract-based nanosystems in the management of the metabolic syndrome. Numerous nano-drug delivery systems, i.e., liposomes, hydrogel nanocomposites, nanoemulsions, micelles, solid lipid, and core-shell nanoparticles, have been designed using plant extracts. It has been found that most of the nano-formulations successfully reduced oxidative stress, insulin resistance, chronic inflammation, and lipid profile in in vitro and in vivo studies as plant extracts interfere with the pathways of metabolic syndrome. Thus, these novel plant-based nanosystems could act as a promising candidate for clinical applications.
    Keywords:  medicinal plants; metabolic disorders; nano drug; nano system; phytochemicals
    DOI:  https://doi.org/10.3389/fbioe.2021.811917
  37. Colloids Surf B Biointerfaces. 2022 Jan 25. pii: S0927-7765(22)00047-9. [Epub ahead of print]213 112364
    Double-crosslinked bifunctional hydrogels with encapsulated anti-cancer drug for bone tumor cell ablation and bone tissue regeneration.
    Shangsi Chen, Yue Wang, Xin Zhang, Jun Ma, Min Wang.
      Many biomaterials are made and studied to provide anticancer therapy, and many other biomaterials have been developed to assist body tissue regeneration. It has been a challenge to design and produce effective multifunctional, or bifunctional, biomaterials for clinical applications to prevent cancer recurrence and, at the same time, to promote new tissue formation after surgical removal of the tumor for millions of cancer patients. In this study, bifunctional UV and Sr2+ double-crosslinked alginate (ALG)/allylated gelatin (GelAGE) hydrogels incorporated with polydopamine (PDA) particles were designed and made. Furthermore, doxorubicin hydrochloride (DOX), an anticancer drug, was incorporated in PDA particles. It was aimed for the new ALG/GelAGE-PDA@DOX hydrogels to exhibit anticancer synergy and hence provide combined chemotherapy and phototherapy (PTT) for bone tumor cell ablation. In vitro experiments using MG63 osteosarcoma cells showed that ALG/GelAGE-PDA@DOX hydrogels could effectively kill tumor cells through the synergy of controlled DOX release and hyperthermia ablation. It was also aimed for the new hydrogels to facilitate bone tissue regeneration at the original bone tumor site. The results of in vitro experiments demonstrated that owing to the release of Sr2+, the new hydrogels could promote the proliferation of rat bone mesenchymal stem cells (rBMSCs) and also the alkaline phosphatase (ALP) activity of cells, indicating their osteogenic promotion ability. The ALG/GelAGE-PDA@DOX hydrogels have therefore exhibited great potential for the treatment of bone tumor-related defects.
    Keywords:  Anti-tumor effect; Bone regeneration; Drug delivery; Hydrogel; Polydopamine
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112364
  38. Expert Opin Drug Metab Toxicol. 2022 Mar 03.
    Are we still on the right Path(way)?: the altered expression of the pentose phosphate pathway in solid tumors and the potential of its inhibition in combination therapy.
    Caroline J W Meskers, Marika Franczak, Ryszard T Smolenski, Elisa Giovannetti, Godefridus J Peters.
       INTRODUCTION: The pentose phosphate pathway (PPP) branches from glycolysis and is crucial for cell growth, since it provides necessary compounds for anabolic reactions, nucleotide synthesis and detoxification of reactive-oxygen-species (ROS). Overexpression of PPP enzymes has been reported in multiple cancer types and linked to therapy resistance, making their inhibition interesting targets for anti-cancer therapies.
    AREAS COVERED: This review summarizes the extent of PPP upregulation across different cancer types, and the non-metabolic functions that PPP-enzymes might contribute to cancer initiation and maintenance. The effects of PPP-inhibition and their combinations with chemotherapeutics are summarized. We searched the databases provided by the University of Amsterdam to characterize the altered expression of the PPP across different cancer types, and to identify the effects of PPP-inhibition.
    EXPERT OPINION: It can be concluded that there are synergistic and additive effects of PPP-inhibition and various classes of chemotherapeutics. These effects may be attributed to the increased susceptibility to ROS. However the toxicity, low efficacy and off-target effects of PPP-inhibitors make application in clinical practice challenging. Novel inhibitors are currently being developed, which could make PPP-inhibition a potential therapeutic strategy in the future, especially in combination with conventional chemotherapeutics and the inhibition of other metabolic pathways.
    Keywords:  NAD/NADH; cancer; chemotherapy; glycolysis; pentose phosphate pathway
    DOI:  https://doi.org/10.1080/17425255.2022.2049234
  39. Front Pharmacol. 2022 ;13 847048
    Mitochondria-Targeting Chemodynamic Therapy Nanodrugs for Cancer Treatment.
    Qiaohui Chen, Niansheng Li, Xiaoyuan Wang, Yuqi Yang, Yuting Xiang, Xingyu Long, Jinping Zhang, Jia Huang, Li Chen, Qiong Huang.
      Mitochondria, as one of the most critical subcellular organelles of cancer cells, are very vulnerable and often on the verge of oxidative stress. The classic chemodynamic therapy (CDT) directly employs endogenous chemical energy to trigger reactive oxygen species (ROS) burst and destroy tumor cells. However, the effectiveness of CDT is restricted by the limited diffusion distance and short half-life of ROS. From this perspective, the treatment method (mitochondria-targeting chemodynamic therapy nanodrugs, M-CDT nanodrugs) that can generate high levels of ROS at the mitochondrial site is extremely efficient and promising for cancer treatment. Currently, many emerging M-CDT nanodrugs have been demonstrated excellent spatial specificity and anti-cancer efficacy. In this minireview, we review various proof-of-concept researches based on different M-CDT nanodrugs designs to overcome the limits of the efficacy of CDT, mainly divided into four strategies: supplying H2O2, non-H2O2 dependent CDT, eliminating GSH and enhancing by hyperthermia therapy (HT). These well-designed M-CDT nanodrugs greatly increase the efficacy of CDT. Finally, the progress and potential of M-CDT nanodrugs are discussed, as well as their limitations and opportunities.
    Keywords:  cancer therapy; chemodynamic therapy; mitochondria-targeting; nanomaterials; reactive oxygen species
    DOI:  https://doi.org/10.3389/fphar.2022.847048
  40. Cell Cycle. 2022 Mar 03. 1-13
    The histidine phosphatase LHPP: an emerging player in cancer.
    Fahong Wu, Hanwei Ma, Xiaoli Wang, Hangzhi Wei, Wei Zhang, Youcheng Zhang.
      Cancers continue to have high incidence and mortality rates worldwide. Therefore, cancer control remains the main public health goal. Growing research evidence suggests that phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) plays an important role in inhibiting tumor cell progression. It has been reported in the literature that LHPP is expressed at low levels in tumor tissues and cells and that patients with low LHPP expression have a poorer prognosis. Functional studies have shown that LHPP can inhibit tumor cell proliferation, metastasis, and apoptosis by affecting different target genes. In addition, researchers have used iDPP nanoparticles to deliver LHPP plasmids to treat tumors, demonstrating the great potential of LHPP plasmids for cancer therapy. In our review, we highlight the biological functions and important downstream target genes of LHPP in tumors, providing a theoretical basis for the treatment of human cancers. Although not thoroughly studied in terms of tumor mechanisms, LHPP still represents a promising and effective anticancer drug target.
    Keywords:  LHPP; mechanism; target genes; tumor
    DOI:  https://doi.org/10.1080/15384101.2022.2044148
  41. Front Oncol. 2021 ;11 835141
    Therapeutic Potential of Glutamine Pathway in Lung Cancer.
    Enyu Tang, Siyang Liu, Zhiming Zhang, Rixin Zhang, Dejing Huang, Tong Gao, Tianze Zhang, Guangquan Xu.
      Cancer cells tend to obtain the substances needed for their development depending on altering metabolic characteristics. Among the reorganized metabolic pathways, Glutamine pathway, reprogrammed to be involved in the physiological process including energy supply, biosynthesis and redox homeostasis, occupies an irreplaceable role in tumor cells and has become a hot topic in recent years. Lung cancer currently maintains a high morbidity and mortality rate among all types of tumors and has been a health challenge that researchers have longed to overcome. Therefore, this study aimed to clarify the essential role of glutamine pathway played in the metabolism of lung cancer and its potential therapeutic value in the interventions of lung cancer.
    Keywords:  glutaminase; glutamine; glutamine transporter; lung cancer; metabolic reprogramming; target
    DOI:  https://doi.org/10.3389/fonc.2021.835141
  42. Biochim Biophys Acta Rev Cancer. 2022 Feb 25. pii: S0304-419X(22)00028-2. [Epub ahead of print] 188703
    Targeting nanoparticles to malignant tumors.
    Nikita Sharma, Kais Bietar, Ursula Stochaj.
      Nanomaterials are at the forefront of health research and development. Among different nanomaterials, nanoparticles are especially promising for cancer theranostics. However, despite great potential, the clinical translation of nano-based applications continues to face obstacles. A major hurdle to the localized eradication of tumors is the efficient targeting of nanomaterials to the desired tissues and cells. In particular, nanoparticle properties and the route of administration impact the efficacy of precision nanomedicine. This review focuses on nanoparticles that have been produced for the detection and treatment of cancer. Common and tissue-specific barriers that limit the accumulation of nanoparticles in malignant tumors are discussed. The in-depth discussion focuses on the physicochemical properties of nanoparticles and the surface modifications that achieve efficient accumulation at tumor sites. Furthermore, limitations of current strategies and open questions are presented. The review concludes with an outlook on future directions and the trajectories that will drive the field forward to advance nano-oncology in the clinic.
    Keywords:  Cancer; Nanomaterials; Nanoparticle targeting; Theranostics
    DOI:  https://doi.org/10.1016/j.bbcan.2022.188703
  43. Front Neurosci. 2021 ;15 806713
    Fabrication and Assessment of Diosgenin Encapsulated Stearic Acid Solid Lipid Nanoparticles for Its Anticancer and Antidepressant Effects Using in vitro and in vivo Models.
    Hina Khan, Sadia Nazir, Rai Khalid Farooq, Ishaq N Khan, Aneela Javed.
      Inflammatory cascade plays a pivotal role in the onset and progression of major depressive disorder (MDD) and glioblastoma multiforme (GBM). Therefore, questing natural compounds with anti-inflammatory activity such as diosgenin can act as a double-edged sword targeting cancer and cancer-induced inflammation simultaneously. The blood-brain barrier limits the therapeutic efficiency of the drugs against intracranial pathologies including depression and brain cancers. Encapsulating a drug molecule in lipid nanoparticles can overcome this obstacle. The current study has thus investigated the anticancer and antidepressant effect of Tween 80 (P80) coated stearic acid solid lipid nanoparticles (SLNPs) encapsulating the diosgenin. Physio-chemical characterizations of SLNPs were performed to assess their stability, monodispersity, and entrapment efficiency. In vitro cytotoxic analysis of naked and drug encapsulated SLNPs on U-87 cell line indicated diosgenin IC50 value to be 194.4 μM, while diosgenin encapsulation in nanoparticles slightly decreases the toxicity. Antidepressant effects of encapsulated and non-encapsulated diosgenin were comprehensively evaluated in the concanavalin-A-induced sickness behavior mouse model. Behavior test results indicate that diosgenin and diosgenin encapsulated nanoparticles significantly alleviated anxiety-like and depressive behavior. Diosgenin incorporated SLNPs also improved grooming behavior and social interaction as well as showed normal levels of neutrophils and leukocytes with no toxicity indication. In conclusion, diosgenin and diosgenin encapsulated solid lipid nanoparticles proved successful in decreasing in vitro cancer cell proliferation and improving sickness behavioral phenotype and thus merit further exploration.
    Keywords:  blood-brain barrier; concanavalin-A; diosgenin; drug delivery; polysorbate-80; sickness mouse model; solid lipid nanoparticles
    DOI:  https://doi.org/10.3389/fnins.2021.806713
  44. Biotechnol Appl Biochem. 2022 Mar 03.
    Zerumbone-induced reactive oxygen species-mediated oxidative stress re-sensitizes breast cancer cells to paclitaxel.
    Jutao Li, Lingying Wang, Yuxin Sun, Zhe Wang, Ye Qian, Vidhya Duraisamy, Tawfiq M Al Antary.
      Chemotherapy is an effective approach for cancer therapy when plant-derived sensitizers are combined with chemotherapeutics. Zerumbone, a natural phytochemical, has been documented to have various pharmacological roles. Here, we evaluated the chemosensitization potential of zerumbone in a breast cancer cell line in vitro. Zerumbone-induced cytotoxicity in MCF-7 cells was assessed by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT)-based metabolic analysis. Reactive oxygen species (ROS)-mediated mitochondrial membrane alterations, DNA damage, and apoptotic morphological changes were measured by fluorescence microscopy methods. A biochemical assay was employed to analyze TBARS and antioxidant levels. Apoptotic marker expression levels were investigated by immunoblotting. MTT assay revealed that zerumbone significantly enhanced paclitaxel (PTX)-induced cell death in breast cancer cells in a concentration-dependent manner. Furthermore, our study demonstrated that zerumbone (15 μM) significantly enhanced ROS when combined with PTX (1 μM) treatment. Additionally, we observed that zerumbone enhanced the impairment of MMP and oxidative DNA damage, thereby inducing apoptosis in combination with PTX. Western blot analysis indicated that zerumbone significantly upregulated BAX, caspase-7, and caspase-9 expression and decreased BCL-2 expression, thereby inducing proapoptotic protein-mediated cell death combined with PTX. The pro-oxidant properties of zerumbone potentially re-sensitize breast cancer cells to PTX by enhancing intracellular ROS-mediated oxidative stress. This article is protected by copyright. All rights reserved.
    Keywords:  apoptosis; breast cancer; paclitaxel; reactive oxygen species; zerumbone
    DOI:  https://doi.org/10.1002/bab.2326
  45. Semin Cancer Biol. 2022 Feb 23. pii: S1044-579X(22)00049-9. [Epub ahead of print]
    Re-establishing the comprehension of phytomedicine and nanomedicine in inflammation-mediated cancer signaling.
    Niraj Kumar Jha, Saniya Arfin, Saurabh Kumar Jha, Rohan Kar, Abhijit Dey, Rohit Gundamaraju, Ghulam Md Ashraf, Piyush Kumar Gupta, Sugapriya Dhanasekaran, Mosleh Mohammad Abomughaid, Sabya Sachi Das, Sachin Kumar Singh, Kamal Dua, Shubhadeep Roychoudhury, Dhruv Kumar, Janne Ruokolainen, Shreesh Ojha, Kavindra Kumar Kesari.
      Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-β/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded nanoparticles have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer.
    Keywords:  Nanomedicine; cancer signaling; cancer therapeutics; inflammation; phytomedicine
    DOI:  https://doi.org/10.1016/j.semcancer.2022.02.022
  46. Chem Biol Interact. 2022 Feb 26. pii: S0009-2797(22)00074-6. [Epub ahead of print]356 109869
    Harnessing the therapeutic potential of fisetin and its nanoparticles: Journey so far and road ahead.
    Sukriti Vishwas, Sachin Kumar Singh, Monica Gulati, Ankit Awasthi, Rubiya Khursheed, Leander Corrie, Rajan Kumar, Trudi Collet, Raimar Loebenberg, Omji Porwal, Saurabh Gupta, Niraj Kumar Jha, Piyush Kumar Gupta, Hari Prasad Devkota, Dinesh Kumar Chellappan, Gaurav Gupta, Jon Adams, Kamal Dua.
      Fisetin (FS) is a bioactive flavonoid obtained mostly from apple and strawberry and classified under the category of food supplements due to numerous pharmacological effects against various diseases through multiple mechanistic pathways. It acts as excellent neuroprotective, cardioprotective, anti-invasive, anti-tumorigenic, anti-angiogenic, anticancer, antidiabetics, antioxidant, anti-inflammatory agent. Despite having excellent safety and efficacy profile, FS is very less explored to clinical research either as food supplement or, as therapeutic agent due to its poor aqueous solubility, low bioavailability and reduced blood brain barrier permeability. Multiple mechanistic pathways through which FS elicits its pharmacological actions and the challenges associated with FS that compromises therapeutic efficacy are described in this article. The nanoformulations developed to enhance the bioavailability and therapeutic efficacy of FS are also covered with detailed description of research works carried by various researchers. These include nanoemulsions, liposomes, ethosomes, glycerosomes, polymeric micelles, self-nanoemulsifying drug delivery system and polymeric nanoparticles. Various patents pertaining to extraction/isolation, formula composition and therapeutic uses of FS as well as some clinical studies conducted using FS as active moiety are also enlisted.
    Keywords:  Antioxidant; Bioavailability; Fisetin; Flavonoid; Novel drug delivery systems
    DOI:  https://doi.org/10.1016/j.cbi.2022.109869
  47. Curr Med Chem. 2022 Mar 01.
    Phytocompounds from the medicinal and dietary plants: Multi-target agents for cancer prevention and therapy.
    Shoaib Shoaib, Najmul Islam, Nabiha Yusuf.
      Cervical cancer is the fourth leading cause of cancer death among women worldwide. Due to cervical cancer's high incidence and mortality, there is an unmet demand for effective diagnostic, therapeutic, and preventive agents. At present, the preferred treatment strategies for advanced metastatic cervical cancer include surgery, radiotherapy, and chemotherapy. However, cervical cancer is gradually developing resistance to chemotherapy, thereby reducing its efficacy. Over the last several decades, phytochemicals, a general term for compounds produced from plants, have gained attention for their role in preventing cervical cancer. This role in cervical cancer prevention has garnered attention on the medicinal properties of fruits and vegetables. Phytochemicals are currently being evaluated for their ability to block proteins involved in carcinogenesis and chemoresistance against cervical cancer. Chemoresistance to cancer drugs like cisplatin, doxorubicin, and 5-fluorouracil has become a significant limitation of drug-based chemotherapy. However, the combination of cisplatin with other phytochemicals has been identified as a promising alternative to subjugate cisplatin resistance. Phytochemicals are promising chemo-preventive and chemotherapeutic agents as they possess antioxidant, anti-inflammatory, and anti-proliferative potential against many cancers, including cervical cancer. Furthermore, the ability of the phytochemicals to modulate cellular signaling pathways through up and down regulation of various proteins has been claimed for their therapeutic potential. Phytochemicals also display a wide range of biological functions, including cell cycle arrest, apoptosis induction, inhibition of invasion, and migration in cervical cancer cells. Numerous studies have revealed the critical role of different signaling proteins and their signaling pathways in the pathogenesis of cervical cancer. Here, we review the ability of several dietary phytochemicals to alter carcinogenesis by modulating various molecular targets.
    Keywords:  apoptosis; carcinogenesis; cervical cancer; chemoresistance; chemotherapeutics; cytotoxicity; oxidative stress; phytochemicals
    DOI:  https://doi.org/10.2174/0929867329666220301114251
  48. Nature. 2022 Mar 02.
    Silent mutations reveal therapeutic vulnerability in RAS Q61 cancers.
    Yoshihisa Kobayashi, Chhayheng Chhoeu, Jiaqi Li, Kristin S Price, Lesli A Kiedrowski, Jamie L Hutchins, Aaron I Hardin, Zihan Wei, Fangxin Hong, Magda Bahcall, Prafulla C Gokhale, Pasi A Jänne.
      RAS family members are the most frequently mutated oncogenes in human cancers. Although KRAS(G12C)-specific inhibitors show clinical activity in patients with cancer1-3, there are no direct inhibitors of NRAS, HRAS or non-G12C KRAS variants. Here we uncover the requirement of the silent KRASG60G mutation for cells to produce a functional KRAS(Q61K). In the absence of this G60G mutation in KRASQ61K, a cryptic splice donor site is formed, promoting alternative splicing and premature protein termination. A G60G silent mutation eliminates the splice donor site, yielding a functional KRAS(Q61K) variant. We detected a concordance of KRASQ61K and a G60G/A59A silent mutation in three independent pan-cancer cohorts. The region around RAS Q61 is enriched in exonic splicing enhancer (ESE) motifs and we designed mutant-specific oligonucleotides to interfere with ESE-mediated splicing, rendering the RAS(Q61) protein non-functional in a mutant-selective manner. The induction of aberrant splicing by antisense oligonucleotides demonstrated therapeutic effects in vitro and in vivo. By studying the splicing necessary for a functional KRAS(Q61K), we uncover a mutant-selective treatment strategy for RASQ61 cancer and expose a mutant-specific vulnerability, which could potentially be exploited for therapy in other genetic contexts.
    DOI:  https://doi.org/10.1038/s41586-022-04451-4
  49. Front Bioeng Biotechnol. 2022 ;10 841186
    Biomimetic Cucurbitacin B-Polydopamine Nanoparticles for Synergistic Chemo-Photothermal Therapy of Breast Cancer.
    Junke Leng, Xiaofeng Dai, Xiao Cheng, Hao Zhou, Dong Wang, Jing Zhao, Kun Ma, Changhao Cui, Li Wang, Zhaoming Guo.
      Breast cancer is the most common malignant tumor in women. Researchers have found that the combined use of multiple methods to treat tumors is a promising strategy. Here, we have developed a biomimetic nano-platform PDA@MB for tumor targeted photothermal therapy (PTT) combined with chemotherapy. The 4T1 cell membrane loaded with cucurbitacin B (CuB) was used to coat polydopamine (PDA) nanoparticles, which gave PDA@MB nanoparticles the ability to target tumors and escape immune cells from phagocytosis. PDA@MB showed excellent photothermal performance including high photothermal conversion efficiency and photostability, and exhibited outstanding in vitro PTT effect under NIR laser irradiation. The high temperature ruptured the PDA@MB membrane to release CuB, which changed the tumor hypoxic environment, down-regulated the FAK/MMP signaling pathway, and significantly inhibited the metastasis and proliferation of tumor cells. The results of in vivo experiments indicated that the tumor growth of the 4T1 mouse tumor model was significantly inhibited. Additionally, toxicity studies showed that PDA@MB had good biocompatibility and safety. In conclusion, this study provides a promising chemo-photothermal therapy (CPT) nano-platform for precise and effective breast cancer therapy.
    Keywords:  biomimetic; cucurbitacin B; photothermal therapy; synergistic treatment; targeted drug delivery
    DOI:  https://doi.org/10.3389/fbioe.2022.841186
  50. Biomed Pharmacother. 2022 Feb 24. pii: S0753-3322(22)00115-9. [Epub ahead of print]148 112727
    Autophagy and cancer: Can tetrandrine be a potent anticancer drug in the near future?
    N Bhagya, K R Chandrashekar.
      Autophagy is an essential catabolic process in mammalian cells to maintain cellular integrity and viability by degrading the old and damaged cell organelles and other contents with the help of lysosomes. Deregulation in autophagy can be one of the major contributors leading to the continuous cell proliferation and development of tumors. Tetrandrine, a bisbenzylisoquinoline alkaloid known to have potent bioactivities such as anticancer, antimicrobial, anti-inflammatory, antidiabetic, antioxidant, immunosuppressive, cardiovascular, and calcium channel blocking effects. The present review evaluated the effectiveness of tetrandrine in targeting key proteins in the autophagy pathway to induce anticancer effect based on the available literature. An attempt is also made to understand the influence of tetrandrine in regulating autophagy by mTOR dependant and mTOR-independent pathways. In addition, the review also highlights the limitations involved and future perspectives in developing tetrandrine as a chemotherapeutic drug to treat cancer.
    Keywords:  Autophagy; Beclin-1; Cancer; MTOR inhibitor; Tetrandrine
    DOI:  https://doi.org/10.1016/j.biopha.2022.112727
  51. Mater Today Bio. 2022 Mar;14 100223
    Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis treatment.
    Mi Zhang, Wenhui Hu, Chenhui Cai, Yu Wu, Jianmei Li, Shiwu Dong.
      Inflammatory arthritis is a major cause of disability in the elderly. This condition causes joint pain, loss of function, and deterioration of quality of life, mainly due to osteoarthritis (OA) and rheumatoid arthritis (RA). Currently, available treatment options for inflammatory arthritis include anti-inflammatory medications administered via oral, topical, or intra-articular routes, surgery, and physical rehabilitation. Novel alternative approaches to managing inflammatory arthritis, so far, remain the grand challenge owing to catastrophic financial burden and insignificant therapeutic benefit. In the view of non-targeted systemic cytotoxicity and limited bioavailability of drug therapies, a major concern is to establish stimuli-responsive drug delivery systems using nanomaterials with on-off switching potential for biomedical applications. This review summarizes the advanced applications of triggerable nanomaterials dependent on various internal stimuli (including reduction-oxidation (redox), pH, and enzymes) and external stimuli (including temperature, ultrasound (US), magnetic, photo, voltage, and mechanical friction). The review also explores the progress and challenges with the use of stimuli-responsive nanomaterials to manage inflammatory arthritis based on pathological changes, including cartilage degeneration, synovitis, and subchondral bone destruction. Exposure to appropriate stimuli induced by such histopathological alterations can trigger the release of therapeutic medications, imperative in the joint-targeted treatment of inflammatory arthritis.
    Keywords:  ACLT, anterior cruciate ligament transection; ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; AIA, adjuvant-induced arthritis; AMF, alternating magnetic field; APCs, antigen-presenting cells; BBR, berberine; CAT, catalase; CD44, cluster of differentiation 44; CEL, tripterine; CEL-PRNPs, RGD-modified PLGA enzyme-responsive nanoparticles loaded with tripterine; CIA, collagen-induced arthritis; CTSK, cathepsin K; CaP, calcium phosphate; Cartilage degeneration; DCF, diclofenac; DEX-P, dexamethasone sodium phosphate; DMARDs, disease-modifying anti-rheumatic drugs; DMM, destabilization of medial meniscus; Dex/Oxi-α CDNPs, 4-phenylborate-cyclodextrin biomaterial loaded with dexamethasone; ECM, extracellular matrix; ELP, elastin-like peptide; ERK1/2, extracellular signal-regulated kinase 1/2; FLSS, fibroblast synovial cells; GPX, glutathione peroxidase; GSH, glutathione; HA, hyaluronic acid; HIFU, high intensity focused ultrasound; HM, hollow microsphere; IBU, ibuprofen; IGF-1, insulin-like growth factor-1; IL, interleukin; IL-1Ra, interleukin-1 receptor antagonist; Inflammatory arthritis; K/BxN, the T cell receptor transgene KRN and the MHC class II molecule; KAFAK, KAFAKLAARLYRKALARQLGVAA; KGN, kartogenin; LDH, lactate dehydrogenase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MFGCN, methotrexate-loaded folate-conjugated glycol chitosan nanoparticles; MHC, major histocompatibility complex; MMPs, matrix metalloproteinases; MNPs, multifunctional nanoparticles; MOF, metal-organic framework; MP-HANPs, mineralized nanoparticles; MPEG-PPF, methoxy polyethylene glycol-polypropylene fumarate; MRI, magnetic resonance imaging; MTX, methotrexate; NADPH, nicotinamide adenine dinucleotide phosphate; NFATc1, nuclear factor of activated T cell cytoplasmic 1; NGPEGSS, nanoparticles with degradable disulfide crosslinks; NIR, near-infrared; NO, nitric oxide; NP, nanoparticle; NP-gel, nanoparticle-hydrogel hybrid system; NSAIDs, non-steroidal anti-inflammatory drugs; Nrf2, nuclear factor erythroid 2-related factor 2; OA, osteoarthritis; P-HA, polyethylene glycol hyaluronic acid; PAMAM, poly (Ninylisobutyramide); PCA, protocatechuic acid; PDEPT, pre-enzyme drug therapy; PDT, photodynamic therapy; PEG-PLGA-Au, polyethylene-glycol polylactic-glycolic acid gold-containing nanoparticles; PEOx-PPOy-PEOz, poly (ethylene oxide)-block-poly (Oxypropylene)-block-poly (ethylene oxide); PEVS, platelet-derived extracellular vesicles; PICsomes, polyion complex vesicles; PLCG1, phospholipase C gamma 1; PLGA, polylactic-glycolic acid; PMEOMA, poly [2-(2-methoxyethoxy) ethylmethacrylate]; PNC, bisphosphonate-modified nanocellulose; PNIPAM, poly (N-isopropyl acrylamide); PON1, paraoxonase-1; POxs, poly (2-oxazoline); PPS, polyphenylene sulfide; PTH, parathyroid hormone; PTT, photothermal therapy; Q, a tripeptide sequence QAW; RA, rheumatoid arthritis; RANKL, nuclear factor-kappa B ligand; RFA, radiofrequency thermal ablation; RGD, arginine-glycine-aspartic acid; RMTQ, RGD-MMP-TAT-QAW peptide; ROS, reactive oxygen species; Redox, reduction-oxidation; SBC, sodium bicarbonate; SOD, superoxide dismutase; SPION, superparamagnetic iron oxide nanoparticles; Stimuli-responsive drug delivery system; Subchondral bone destruction; Synovitis; T cell, thymus cell; T, cell-penetrating peptide; TA, triamcinolone acetonide; TAT, transcription-transactivating; TATQ, TAT-QAW; TG-18, triglycerol monostearate; TIMP, tissue inhibitor of metalloproteinase; TNF, tumor necrosis factor; TR1, type 1 regulatory; TolDex, tolerogenic dendritic cell-derived exosomes; US, ultrasound; VEGF, vascular endothelial growth factor; fMRI, focusing magnetic resonance imaging; β-TCP, β-tricalcium phosphate
    DOI:  https://doi.org/10.1016/j.mtbio.2022.100223
  52. Expert Opin Drug Deliv. 2022 Mar 01. 1-21
    Recent advances in targeted drug delivery for the treatment of pancreatic ductal adenocarcinoma.
    Haolin Song, Chen Jiang.
       INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has become a serious health problem with high impact worldwide. The heterogeneity of PDAC makes it difficult to apply drug delivery systems (DDS) used in other cancer models, for example, the poorly developed vascular system makes anti-angiogenic therapy ineffective. Due to its various malignant pathological changes, drug delivery against PDAC is a matter of urgent concern. Based on this situation, various drug delivery strategies specially designed for PDAC have been generated.
    AREAS COVERED: This review will briefly describe how delivery systems can be designed through nanotechnology and formulation science. Most research focused on penetrating the stromal barrier, exploiting and alleviating the hypoxic microenvironment, targeting immune cells, or designing vaccines, and combination therapies. This review will summarize the ways to reverse the malignant pathological features of PDAC and hopefully provide ideas for subsequent studies.
    EXPERT OPINION: Drug delivery systems designed to achieve penetrating functions or to alleviate hypoxia and activate immunity have achieved good therapeutic results in animal models in several studies. In future studies, there is a need to deliver PDAC therapeutics in a more precise manner, or the use of drug carriers for multiple functions simultaneously, are potential therapeutic strategy.
    Keywords:  Drug delivery systems; Harnessing the hypoxia microenvironment; Pancreatic ductal adenocarcinoma; Re-education of the immune microenvironment; Stromal barriers penetration
    DOI:  https://doi.org/10.1080/17425247.2022.2045943
  53. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2022 Feb 25. 39(1): 207-216
    [Research progress about photothermal nanomaterials with targeted antibacterial properties and their applications in wound healing].
    Xiangnan Yuan, Shaojie Tan, Jing Gao, Lu Wang.
      With the development of photothermal nanomaterials, photothermal therapy based on near-infrared light excitation shows great potential for the bacterial infected wound treatment. At the same time, in order to improve the photothermal antibacterial effect of wound infection and reduce the damage of high temperature and heat to healthy tissue, the targeted bacteria strategy has been gradually applied in wound photothermal therapy. In this paper, several commonly used photothermal nanomaterials as well as their targeted bacterial strategies were introduced, and then their applications in photothermal antibacterial therapy, especially in bacterial infected wounds were described. Besides, the challenges of targeted photothermal antibacterial therapy in the wound healing application were analyzed, and the development of photothermal materials with targeted antibacterial property has prospected in order to provide a new idea for wound photothermal therapy.
    Keywords:  Bacterial infection; Photothermal antibacterial properties; Photothermal nanomaterials; Targeted bacteria; Wound healing
    DOI:  https://doi.org/10.7507/1001-5515.202103022
  54. BMC Microbiol. 2022 Mar 04. 22(1): 68
    Theranostic nanoplatforms of emodin-chitosan with blue laser light on enhancing the anti-biofilm activity of photodynamic therapy against Streptococcus mutans biofilms on the enamel surface.
    Maryam Pourhajibagher, Nasrin Keshavarz Valian, Abbas Bahador.
       BACKGROUND: Combining photosensitizer and light irradiation, named antimicrobial photodynamic therapy (aPDT) is an adjuvant therapy for eliminating microbial biofilms. This ex vivo study evaluates the effect of anti-biofilm activity of aPDT based on emodin-chitosan nanoparticles (Emo-CS-NPs) plus blue laser light against Streptococcus mutans biofilm on the enamel surface.
    MATERIALS: After determination of the fractional inhibitory concentration index of Emo and CS by checkerboard array assay, Emo-CS-NPs were synthesized and characterized. Following treatment of pre-formed S. mutans biofilms on the enamel slabs, cellular uptake of Emo-CS-NPs and intracellular reactive oxygen species (ROS) production were determined. The anti-biofilm and anti-metabolic activities of aPDT were investigated. Eventually, lactic acid production capacity, concentrations of S. mutans extracellular DNA (eDNA) levels, and expression of the gene involved in the biofilm formation (gtfB) were evaluated.
    RESULTS: The maximum uptake of Emo-CS-NPs occurs in an incubation time of 5 min. When irradiated, Emo-CS-NPs were photoactivated, generating ROS, and led to a decrease in the cell viability and metabolic activity of S. mutans significantly (P < 0.05). S. mutans eDNA and lactic acid production outcomes indicated that Emo-CS-NPs-mediated aPDT led to a significant reduction of eDNA levels (48%) and lactic acid production (72.4%) compared to the control group (P < 0.05). In addition, gtfB mRNA expression in S. mutans was downregulated (7.8-fold) after aPDT in comparison with the control group (P < 0.05).
    CONCLUSIONS: Our data support that, aPDT using Emo-CS-NPs revealed the highest cellular uptake and ROS generation. Emo-CS-NPs based aPDT could inhibit significantly biofilm formation and reduce effectively virulence potency of S. mutans; thus, it could be an adjuvant therapy against dental caries.
    Keywords:  Antimicrobial photodynamic therapy; Biofilms; Chitosan; Emodin; Streptococcus mutans
    DOI:  https://doi.org/10.1186/s12866-022-02481-6
  55. Biomater Sci. 2022 Mar 01.
    Mesoporous silica nanoparticle-supported nanocarriers with enhanced drug loading, encapsulation stability, and targeting efficiency.
    Jun Yong Oh, Gyeongseok Yang, Eunshil Choi, Ja-Hyoung Ryu.
      For efficient drug delivery, stable encapsulation of a large amount of anticancer drugs is crucial, not to mention cell-specific delivery. Among many possible nanocarriers, mesoporous silica nanoparticles are versatile frameworks that satisfy those requirements owing to their characteristic internal pores with a large surface area and a tunable surface composition. By using a noncovalent post-modification strategy, MSN-based drug delivery systems with enhanced therapeutic efficiency can be prepared in a simple one-pot process by loading small anticancer drugs in the unmodified mesopores and by subsequently blocking the drug-loaded pores with a stimuli-responsive polymer gatekeeper. For targeted delivery, drug-loaded MSNs can be functionalized with suitable targeting components such as targeting ligands or artificial protein corona. This mini-review highlights the recent research in which MSN-supported nanocarriers are designed, synthesized, and characterized to possess a high drug loading capacity and encapsulation stability along with targeting capability for more efficient cancer treatment.
    DOI:  https://doi.org/10.1039/d2bm00010e
  56. Life Sci. 2022 Feb 27. pii: S0024-3205(22)00139-4. [Epub ahead of print] 120439
    Docetaxel and 5-FU enhanced the inhibitory effects of apatinib and ramucirumab on growth and migration of gastric cancer.
    Jia-Qi Wu, Ruo-Yue Fan, Jing Zhai, Chong-Yong Li, Ping Wei, Li-Zong Shen, Ming-Fang He, Ping Wang, Xin-En Huang.
       BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in the world. The clinical benefit of anti-angiogenic strategy as a single drug is limited. Some studies showed that the combination of anti-angiogenic therapy and chemotherapy exhibited synergistic effect and reduced the side effects of chemotherapy drugs. We investigated the combined effects of these two types of drugs in gastric cancer cells in vitro and in vivo.
    METHODS: cell viability, migration, invasion, and apoptosis were evaluated by CCK8, wound-healing, transwell, and Annexin V-FITC assay, respectively. In vivo anti-cancer efficacy was tested for the cell proliferation and metastasis in cell line derived tumor xenograft (CDX) model and patient derived tumor xenografted (PDX) model based on Tg (fli-1: EGFP) zebrafish embryos; RESULTS: In the cell experiments, the combination of the two types of drugs could inhibit the proliferation and metastasis of gastric cancer cells and promote apoptosis through VEGFR2/AKT/ERK1/2 signal. In the zebrafish CDX (zCDX) model and zebrafish PDX (zPDX) model, the combination of the two treatment also showed a synergistic effect in inhibiting gastric cancer cell metastasis and cell proliferation.
    CONCLUSIONS: Apatinib/ramucirumab targeted therapy combined with docetaxel or 5-fluorouracil (5-FU) may serve as an effective treatment strategy for patients with advanced gastric cancer.
    Keywords:  Anti-angiogenic therapy; Combined treatment; Gastric cancer; Zebrafish; zPDX
    DOI:  https://doi.org/10.1016/j.lfs.2022.120439
  57. J Ethnopharmacol. 2022 Feb 25. pii: S0378-8741(22)00181-7. [Epub ahead of print] 115143
    Ethnomedical, phytochemical and pharmacological insights on an Indian medicinal plant: The balloon vine (Cardiospermum halicacabum Linn.).
    Abbirami Elangovan, Jeyadevi Ramachandran, Dinesh Kumar Lakshmanan, Guna Ravichandran, Sivasudha Thilagar.
       ETHNOPHARMACOLOGICAL RELEVANCE: Cardiospermum halicacabum Linn. (C. halicacabum) is one of the well-known leafy green vegetables in India. It is an herbaceous climber from the Sapindaceae family which is found in almost every Continent and Oceania. In the traditional Indian medicine systems, this plant is used for the treatment of rheumatism, abdominal pain, orchitis, dropsy, lumbago, skin diseases, cough, nervous disorders, and hyperthermia.
    AIM OF THE REVIEW: This review presents the current information about ethnomedical uses and progress on geographical distribution, pharmacological activities, phytochemistry, micropropagation, and toxicity of C. halicacabum. Also, critically summarizes the relationship between the reported pharmacological activities and the traditional usages along with the future perspectives for research on this medicinal plant.
    MATERIALS AND METHODS: The data on C. halicacabum were collected using multiple internet sources such as Google Scholar, Science Direct, Taylor & Francis, PubMed, Web of Science, Springer Link, Wiley online, and plant databases.
    RESULTS: Chemical characterization using LC-MS/MS, HPLC, and NMR exposed the presence of chlorogenic acid, caffeic acid, coumaric acid, luteolin-7-o-glucuronide, apigenin-7-o-glucuronide, and chrysoeriol in different parts of C. halicacabum. Based on the outcomes of this review, the main bioactive compounds found in C. halicacabum include phenols, phenolic acids, flavonoids, flavonoid glycosides, and flavonoid glucuronides. Besides the above-mentioned constituents, palmitic acid, oleic acid, stearic acid, linolenic acid, eicosenoic acid, and arachidic acid are the compounds that constitute the fatty acid profile of C. halicacabum seeds. Specifically, Cardiospermin, a bioactive compound isolated from the root extract of C. halicacabum has been recognized for its anxiolytic activity. Moreover, C. halicacabum showed a broad spectrum of pharmacological activities including anti-inflammatory, anti-arthritic, anti-diabetic, anxiolytic activity, antiulcer, apoptotic activity, antibacterial, antiviral, anti-diarrheal, antioxidant, hepatoprotective, and nephroprotective properties. However, the bioactive compounds responsible for most of the above therapeutic properties have not been elucidated till now.
    CONCLUSION: Phytochemicals from C. halicacabum showed noticeable pharmacological effects against plethora of health disorders. Some of the traditional applications were supported by modern scientific studies, however, more pharmacological evaluations should be conducted to validate other traditional uses of C. halicacabum. Despite C. halicacabum's vast pharmacological activity, additional human clinical trials are needed to determine the potent and safe dosages for the treatment of various health abnormalities. Besides, bioassay-guided isolation of active constituents, pharmacokinetic evaluations and identification of their mode of action are recommended for future investigations on C. halicacabum to unveil its therapeutic drug leads. Overall, this review suggests that C. halicacabum could be a new source of functional foods.
    Keywords:  Anti-arthritic; Anti-inflammatory; Auto-immune disorders; Cardiospermum halicacabum; Functional foods; Medicinal plants
    DOI:  https://doi.org/10.1016/j.jep.2022.115143
  58. Genes Dis. 2022 Mar;9(2): 334-346
    Ferroptosis: An emerging therapeutic opportunity for cancer.
    Liyuan Wang, Xiaoguang Chen, Chunhong Yan.
      Ferroptosis, a new form of non-apoptotic, regulated cell death characterized by iron dependency and lipid peroxidation, is involved in many pathological conditions such as neurodegenerative diseases, heart ischemia/reperfusion injury, acute renal failure, and cancer. While metabolic dysfunctions can lead to excessive lipid peroxidation culminating in ferroptotic cell death, glutathione peroxidase 4 (GPX4) resides in the center of a network that functions to prevent lipid hydroperoxides from accumulation, thereby suppressing ferroptosis. Indeed, RSL3 and other small-molecule GPX4 inhibitors can induce ferroptosis in not only cultured cancer cells but also tumor xenografts implanted in mice. Similarly, erastin and other system Xc- inhibitors can deplete intracellular glutathione required for GPX4 function, leading to lipid peroxidation and ferroptosis. As therapy-resistant cancer cells are sensitive to GPX4-targeted therapeutic regimens, the agents capable of inducing ferroptosis hold great promises to improve current cancer therapy. This review will outline the molecular basis of ferroptosis, but focus on the strategies and the agents developed in recent years for therapeutic induction of ferroptosis. The potentials of these ferroptosis-inducing agents, which include system Xc- inhibitors, GPX4 inhibitors, and iron-based nanoparticles, in cancer therapy will be subsequently discussed.
    Keywords:  Cancer therapy; Erastin; Ferroptosis; GPX4; Lipid peroxidation; Nanomedicine; RSL3; System Xc-
    DOI:  https://doi.org/10.1016/j.gendis.2020.09.005
  59. Int J Biol Macromol. 2022 Feb 24. pii: S0141-8130(22)00342-7. [Epub ahead of print]206 159-166
    Controlled release of 5-fluorouracil to melanoma cells using a hydrogel/micelle composites based on deoxycholic acid and carboxymethyl chitosan.
    Zahra Pourmanouchehri, Sayeh Ebrahimi, Mazdak Limoee, Fereshteh Jalilian, Sajad Janfaza, Amirhossein Vosoughi, Leila Behbood.
      5-Fluorouracil (5-FU) is an antimetabolite drug widely used for the treatment of skin cancer. Despite its proven efficacy in treating malignancies, its systemic administration is limited due to severe side effects. To address this issue, topical delivery of 5-FU has been proposed as an alternative approach for the treatment of skin cancer, however, the poor permeability of 5-FU through the skin is still a challenge. Here, we introduced a pH-responsive micellar hydrogel system based on deoxycholic acid micelle (DCA Mic) and carboxymethyl chitosan hydrogel (CMC Hyd) to enhance 5-FU efficacy against skin cancer and reduce its systemic side effects by improving its delivery into the skin. The properties of the Mic/Hyd system were determined by Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), zeta sizer, atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Drug release studies showed pH-dependent properties of the Hyd. The final formulation was demonstrated to have enhanced anticancer activity than 5-FU against the growth of melanoma cells. The 5-FU@Mic-Hyd could be a promising delivery platform with enhanced efficacy in the management of skin cancer without systemic toxicity.
    Keywords:  5-Fluorouracil; Anticancer; Controlled release; Deoxycholic acid; Micelle
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.02.096
  60. Biomed Mater. 2022 Mar 02.
    A Review: Potential Application and Outlook of Photothermal Therapy in Oral Cancer Treatment.
    Liren Cao, Yongzhi Wu, Yue Shan, Bowen Tan, Jinfeng Liao.
      As one of the most common malignant tumors, oral cancer threatens people's health worldwide. However, traditional therapies, including surgery, radiotherapy, and chemotherapy can't meet the requirement of cancer cure. Photothermal therapy (PTT) has attracted widespread attentions for its advantages of the noninvasive process, few side effects, and promising tumor ablation. Up to now, three types of photothermal agents (PTAs) have been widely employed in oral cancer therapies, which involve metallic materials, carbon-based materials, and organic materials. Previous research mainly introduced hybrid materials due to benefits from the synergistic effect of multiple functions. In this review, we present the advancement of each type PTAs for oral cancer treatment in recent years. In each part, we introduce the properties and synthesis of each PTA, summarize the current studies, and analyze their potential applications. Furthermore, we discuss the status quo and the deficiencies hindering the clinical application of PTT, based on which gives the perspective of its future developing directions.
    Keywords:  combinational therapy; oral cancer; photothermal therapy; potential application; tumor targeting
    DOI:  https://doi.org/10.1088/1748-605X/ac5a23
  61. Phytother Res. 2022 Feb 28.
    A review on the potential use of natural products in overweight and obesity.
    Xin Li, Yu Zhang, Shuxuan Wang, Caihong Shi, Shuang Wang, Xin Wang, Xin Lü.
      With the increase in unhealthy lifestyles, obesity is increasingly common, which could cause many metabolic diseases. In recent research, natural product extracts have shown tremendous potential antiobesity effects via different mechanisms. In this review, we focused on widely adopted extraction methods, bioactive ingredients types, and antiobesity mechanisms of natural product extracts in the recent reports. The extraction methods include solid-liquid extraction, microwave-assisted extractions, and supercritical fluid extraction. Moreover, the bioactive ingredients identified in natural product extracts are phenolic compounds, oligosaccharides, polysaccharides, and terpenoids. These exert antiobesity effects through multiple mechanisms, including suppressing the appetite, increasing energy expenditure, inhibiting enzyme activity, modulating lipid homeostasis and adipocyte lifecycle, reducing oxidative and inflammation, and improving intestinal bacteria. However, the antiobesity effects of natural products require further evaluation. Furthermore, the improvement of the bioavailability and effective and safe human dose of these bioactive ingredients should be the focus of future work.
    Keywords:  antiobesity; extraction methods; mechanisms; natural product; obesity; overweight
    DOI:  https://doi.org/10.1002/ptr.7426
  62. Biochem Biophys Res Commun. 2022 Jan 31. pii: S0006-291X(22)00152-8. [Epub ahead of print]601 101-108
    Shielded geomagnetic field accelerates glucose consumption in human neuroblastoma cells by promoting anaerobic glycolysis.
    Guo-Mi Wang, Jing-Peng Fu, Wei-Chuan Mo, Hai-Tao Zhang, Ying Liu, Rong-Qiao He.
      A shielded geomagnetic field, also called the hypomagnetic field (HMF), interferes with the metabolic processes of various cells and animals exhibiting diverse effects in different models, however, its underlying mechanism remains largely unknown. In this study, we assessed the effect on the energy metabolism of SH-SY5Y cells in HMF and found that HMF-induced cell proliferation depends on glucose supply. HMF promoted SH-SY5Y cell proliferation by increasing glucose consumption rate via up-regulating anaerobic glycolysis in the cells. Increased activity of LDH, a key member of glycolysis, was possibly a direct response to HMF-induced cell proliferation. Thus, we unveiled a novel subcellular mechanism underlying the HMF-induced cellular response: the up-regulation of anaerobic glycolysis and repression of oxidative stress shifted cellular metabolism more towards the Warburg effect commonly observed in cancer metabolism. We suggest that cellular metabolic profiles of various cell types may determine HMF-induced cellular effects, and a magnetic field can be applied as a non-invasive regulator of cell metabolism.
    Keywords:  Cell metabolism; Cell proliferation; Glycolysis; Hypomagnetic field
    DOI:  https://doi.org/10.1016/j.bbrc.2022.01.114
  63. Front Biosci (Landmark Ed). 2022 Feb 12. 27(2): 57
    Potential applications of cocoa (Theobroma cacao) on diabetic neuropathy: mini-review.
    Rebeca Kababie-Ameo, Griselda Mericia Rabadán-Chávez, Natalia Vázquez-Manjarrez, Gabriela Gutiérrez-Salmeán.
      Diabetes Mellitus is a highly prevalent disease in Mexico and in the world, among whose complications is diabetic neuropathy. DN is a group of disorders that present signs and/or symptoms of peripheral nerve dysfunction and have different clinical manifestations in both peripheral neuropathy and autonomic neuropathy. As a part of the mechanisms by which DN develops, oxidative stress and inflammation have been described. Cocoa is a plant origin product which includes around 300 components and through different studies, it has been suggested that cocoa has different mechanisms of action through which exerts its beneficial effects on health. It has been proposed that cocoa has hypoglycemic, lipid-lowering, antioxidant and anti-inflammatory effects, and thus, potentially have a beneficial direct or indirect effect on diabetic neuropathy. Specially in preclinical studies, the anti-inflammatory and anti-nociceptive effect of cocoa has been evaluated through different mechanisms of action. However, most of the studies presented concerning this complication, are in vitro or preclinical studies, so there is still a great area of opportunity regarding the use of cocoa on diabetic neuropathy.
    Keywords:  Cacao; Cocoa; Diabetic neuropathy; Inflammation; Oxidative stress
    DOI:  https://doi.org/10.31083/j.fbl2702057
  64. Expert Opin Drug Deliv. 2022 Mar 04.
    Anticancer nanomedicines harnessing tumor microenvironmental components.
    Yinggang Li, Zhonglan Chen, Lei Gu, Zhengyu Duan, Dayi Pan, Zhuping Xu, Qiyong Gong, Youping Li, Hongyan Zhu, Kui Luo.
       INTRODUCTION: Small-molecular drugs are extensively used in cancer therapy, while they have issues of nonspecific distribution and consequent side effects. Nanomedicines that incorporate chemotherapeutic drugs have been developed to enhance the therapeutic efficacy of these drugs and reduce their side effects. One of the promising strategies is to prepare nanomedicines by harnessing the unique tumor microenvironment (TME).
    AREAS COVERED: The TME contains numerous cell types that specifically express specific antibodies on the surface including tumor vascular endothelial cells, tumor-associated adipocytes, tumor-associated fibroblasts, tumor-associated immune cells and cancer stem cells. The physicochemical environment is characterized with a low pH, hypoxia, and a high redox potential resulting from tumor-specific metabolism. The intelligent nanomedicines can be categorized into two groups: the first group which is rapidly responsive to extracellular chemical/biological factors in the TME and the second one which actively and/or specifically targets cellular components in the TME.
    EXPERT OPINION: In this paper, we review recent progress of nanomedicines by harnessing the TME and illustrate the principles and advantages of different strategies for designing nanomedicines, which are of great significance for exploring novel nanomedicines or translating current nanomedicines into clinical practice. We will discuss the challenges and prospects of preparing nanomedicines to utilize or alter the TME for achieving effective, safe anticancer treatment.
    Keywords:  nanomedicine; stimuli-responsive drug delivery systems; tumor immunosuppressive microenvironment; tumor microenvironment
    DOI:  https://doi.org/10.1080/17425247.2022.2050211
  65. Crit Rev Food Sci Nutr. 2022 Mar 03. 1-31
    Bioactive compounds: Application of albumin nanocarriers as delivery systems.
    Flavia F Visentini, Adrián A Perez, Liliana G Santiago.
      Enriched products with bioactive compounds (BCs) show the capacity to produce a wide range of possible health effects. Most BCs are essentially hydrophobic and sensitive to environmental factors; so, encapsulation becomes a strategy to solve these problems. Many globular proteins have the intrinsic ability to bind, protect, encapsulate, and introduce BCs into nutraceutical or pharmaceutical matrices. Among them, albumins as human serum albumin (HSA), bovine serum albumin (BSA), ovalbumin (OVA) and α-lactalbumin (ALA) are widely abundant, available, and applied in many industrial sectors, becoming promissory materials to encapsulate BCs. Therefore, this review focuses on researches about the main groups of natural origin BCs (namely phenolic compounds, lipids, vitamins, and carotenoids), the different types of nanostructures based on albumins to encapsulate them and the main fields of application for BCs-loaded albumin systems. In this context, phenolic compounds (catechins, quercetin, and chrysin) are the most extensively BCs studied and encapsulated in albumin-based nanocarriers. Other extensively studied subgroups are stilbenes and curcuminoids. Regarding lipids and vitamins; terpenes, carotenoids (β-carotene), and xanthophylls (astaxanthin) are the most considered. The main application areas of BCs are related to their antitumor, anti-inflammatory, and antioxidant properties. Finally, BSA is the most used albumin to produced BCs-loaded nanocarriers.
    Keywords:  Bioactive compounds; albumins; lipids; nanoparticles; phenolic compounds; vitamins and carotenoids
    DOI:  https://doi.org/10.1080/10408398.2022.2045471
  66. Biomaterials. 2022 Feb 17. pii: S0142-9612(22)00067-9. [Epub ahead of print]283 121428
    Immunogenic nanomedicine based on GSH-responsive nanoscale covalent organic polymers for chemo-sonodynamic therapy.
    Fengyun Shen, Danlei Tao, Rui Peng, Yao He, Zhuang Liu, Jiansong Ji, Liangzhu Feng.
      Sonodynamic therapy (SDT) is emerging as a non-invasive strategy to eradicate tumors, but its therapeutic efficacy is still not ideal. To achieve more effective SDT, water insoluble sonosensitizer meso-5, 10, 15, 20-tetra(4-hydroxylphenyl)porphyrin (THPP) is here esterified with succinic acid conjugated oxaliplatin prodrug (Oxa(IV)SA2) and carboxyl group terminated PEG (PEG5k-COOH). The obtained covalent organic polymer (COP) of THPP-Oxa(IV)-PEG with good physiological stability, sonosensitization efficacy and glutathione (GSH) responsive oxalipatin responsive behaviors can induce effective immunogenic cancer cell death upon the ultrasound exposure. In addition, THPP-Oxa(IV)-PEG is shown to be a versatile carrier for both hydrophobic near infrared dye and radioisotope 99mTc, thereby enabling real-time tracking of its pharmacokinetics behavior under corresponding imaging facilities. Furthermore, treatment with THPP-Oxa(IV)-PEG injection and ultrasound exposure is shown to be most effectively in suppressing tumor growth, with 3 of 6 CT26 tumor bearing mice fully cured, ascribing to its high potency in eliciting profound antitumor immune responses. This work highlights a promising strategy in constructing multifunctional nanosonosensitizer as a potent immunogenic nanomedicine to enhance the treatment outcome of SDT.
    Keywords:  Chemo-sonodynamic therapy; Covalent-organic polymers; Immunogenic nanomedicine; Oxaliplatin prodrug
    DOI:  https://doi.org/10.1016/j.biomaterials.2022.121428
  67. J Mater Sci Mater Med. 2022 Mar 04. 33(3): 28
    The ascension of nanosponges as a drug delivery carrier: preparation, characterization, and applications.
    Kartik Tiwari, Sankha Bhattacharya.
      Nanosponges are nanosized drug carriers with a three-dimensional structure created by crosslinking polymers. They have the advantage of being able to hold a wide range of drugs of various sizes. Nanosponges come in a variety of shapes and sizes. They are distinguished by the research method used, the type of polymer used, and the type of drug they may contain. Nanosponges are superior to other delivery systems because they can provide a controlled drug release pattern with targeted drug delivery. The period of action, as well as the drug's residence time, may be regulated. Since it is made of biodegradable materials, it has a low toxicity and is safe to use. The efficiency of drug encapsulation is determined by the size of the drug molecule and the amount of void space available. Cancer, enzyme and biocatalyst carrier, oxygen delivery, solubility enhancement, enzyme immobilization, and poison absorbent are some of the applications for nanosponges. The method of preparation, characterization, factors affecting nanosponge development, drug loading and release mechanism, recent developments in this area, and patents filed in the area of nanosponges are all highlighted in this study. Graphical abstract.
    DOI:  https://doi.org/10.1007/s10856-022-06652-9
  68. Crit Rev Food Sci Nutr. 2022 Mar 02. 1-19
    Stilbenes: Characterization, bioactivity, encapsulation and structural modifications. A review of their current limitations and promising approaches.
    Silvia Navarro-Orcajada, Irene Conesa, Francisco José Vidal-Sánchez, Adrián Matencio, Lorena Albaladejo-Maricó, Francisco García-Carmona, José Manuel López-Nicolás.
      Stilbenes are phenolic compounds naturally synthesized as secondary metabolites by the shikimate pathway in plants. Research on them has increased in recent years due to their therapeutic potential as antioxidant, antimicrobial, anti-inflammatory, anticancer, cardioprotective and anti-obesity agents. Amongst them, resveratrol has attracted the most attention, although there are other natural and synthesized stilbenes with enhanced properties. However, stilbenes have some physicochemical and pharmacokinetic problems that need to be overcome before considering their applications. Human clinical evidence of their bioactivity is still controversial due to this fact and hence, exhaustive basis science on stilbenes is needed before applied science. This review gathers the main physicochemical and biological properties of natural stilbenes, establishes structure-activity relationships among them, emphasizing the current problems that limit their applications and presenting some promising approaches to overcome these issues: the encapsulation in different agents and the structural modification to obtain novel stilbenes with better features. The bioactivity of stilbenes should move from promising to evident.
    Keywords:  Stilbenes; activity; encapsulation; physicochemical; structure; synthesis
    DOI:  https://doi.org/10.1080/10408398.2022.2045558
  69. Front Oncol. 2022 ;12 805978
    Recent Advances in Nanoplatforms for the Treatment of Osteosarcoma.
    Kunzhe Wu, Beibei Yu, Di Li, Yangyang Tian, Yan Liu, Jinlan Jiang.
      Osteosarcoma (OS) is the most common primary bone tumor in children and young people. Traditional surgical excision combined with chemotherapy presents many limitations, such as resistance and systemic side effects of chemotherapy drugs, postoperative recurrence, and bone defects. Given these limitations, novel therapeutic modalities for OS treatment using nanometer-sized platform-based chemotherapeutic delivery have emerged as a promising alternative therapy. This form of therapy offers multiple advantages, such as accurate delivery of the drug to the tumor site and repair of limited bone defects after tumor resection. In this review, we briefly summarize nanoplatforms, including liposomes, polymeric nanoparticles, inorganic nanoparticles, nanomicelles, dendrimers, nanocapsules, and exosomes. The essential shortcomings involved in these nanoplatforms, such as poor stability, immunogenicity, insufficient circulation, and drug leakage are also discussed, and related solutions are briefly proposed. Finally, the application prospects of nanoplatforms in the treatment of OS are discussed.
    Keywords:  drug delivery system; nanoparticles; nanoplatform; osteosarcoma; tumor targeted therapy
    DOI:  https://doi.org/10.3389/fonc.2022.805978
  70. Math Biosci Eng. 2022 Jan 17. 19(3): 2985-2995
    A mathematical model for imaging and killing cancer cells by using concepts of the Warburg effect in designing a Graphene system.
    Massimo Fioranelli, Hijaz Ahmad, Alireza Sepehri, Maria Grazia Roccia, Faissal Aziz.
      According to the Warburg effect, there are some significant differences between metabolisms, products and process of respirations of cancer cells and normal cells. For example, normal cells absorb oxygen and glucose and give water molecules, carbon dioxide, ATP molecules and some number of spinors; while cancer cells take glucose and give lactate, less number of ATP molecules and different number of spinors. Using this property, we can design a system from two graphene sheets that are connected by pairing the fourth free electrons of carbons. Then, we can break some pairs and produce some holes. The number of these holes should be equal to the number of radiated spinors by normal cells. Near a normal cell, all holes are filled and the graphene system doesn't emit any electrical current or wave. However, near a cancer cell, some extra holes or spinors remain that their motions produce some electrical currents. These currents force on cancer cell membranes and destroy them and consequently, cause the cell death. Also, these currents emit some electromagnetic waves which detectors could take them out of the human's body and consequently, they could play the main role in imaging.
    Keywords:   Warburg effect ; cancer ; graphene ; imaging ; quantum
    DOI:  https://doi.org/10.3934/mbe.2022137
  71. Anal Chem. 2022 Feb 27.
    pH-Sensitive Bioprobe for Multichannel Mitochondrial Imaging and Photodynamic Therapy.
    Lu Zhang, Feng-Lei Jiang, Qing-Lian Guo, Yi Liu, Peng Jiang.
      Tumor targeting therapy and photodynamic therapy are effective anti-cancer therapies. Their research progress has attracted wide attention and is one of the focuses of anti-cancer drug research and development. The design and synthesis of multifunctional organic phototheranostic agents for superior image-guided diagnosis and phototherapy play an increasingly positive role in cancer diagnosis and treatment. Herein, F16M and CyM were obtained through functional design from cyanine and F16. Physicochemical characterization and biological application results showed that CyM is a multifunctional organic biological probe, which can realize intracellular multichannel (green, yellow, red, and NIR) imaging, pH detection, and mitochondrial-targeted photodynamic therapy. As an organic phototheranostic agent, it could not only realize near-infrared imaging and photodynamic therapy in vivo and in vitro but also has excellent biocompatibility and good guiding significance for the development of multichannel imaging and mitochondrial-targeting photodynamic therapy.
    DOI:  https://doi.org/10.1021/acs.analchem.2c00306
  72. Front Bioeng Biotechnol. 2022 ;10 804513
    The Apoptosis of Liver Cancer Cells Promoted by Curcumin/TPP-CZL Nanomicelles With Mitochondrial Targeting Function.
    Wanyu Li, Yanan Chen, Kun He, Tianshou Cao, Daibo Song, Huiling Yang, Li Li, Jiantao Lin.
      The mitochondrion is one of the most important cellular organelles, and many drugs work by acting on mitochondria. Curcumin (Cur)-induced apoptosis of HepG2 in liver cancer cells is closely related to the function of inhibiting mitochondria. However, the mitochondrion-targeting curcumin delivery system was rarely been reported. It is important to develop a high-efficiency mitochondrion-targeting curcumin vector that can deliver curcumin into mitochondria directly. Here, a special mitochondrion-targeting delivery system based on triphenylphosphine bromide (TPP)-chitosan-g-poly-(N-3-carbobenzyloxy-l-lysine) (CZL) with TPP functional on the surface is designed to perform highly efficient mitochondria-targeting delivery for effective liver cancer cell killing in vitro. The TEM images showed that the nanomicelles were spherical; the results of fluorescence test showed that TPP-CZL nanomicelles could promote the cellular uptake of drugs and finally targeted to the mitochondria. The results of cell survival rate and Hoechst staining showed that curcumin/TPP-CZL nanomicelles could promote the apoptosis of liver cancer cells. Curcumin/TPP-CZL nanomicelles could significantly reduce the mitochondrial membrane potential, increase the expression of pro apoptotic protein Bcl-2, and reduce the expression of antiapoptotic Bax protein, and these results were significantly better than curcumin/CZL nanomicelles and curcumin. It is a potential drug delivery system with high efficiency to target mitochondria of liver cancer cells.
    Keywords:  TPP; curcumin; liver cancer; mitochondrial; targeted
    DOI:  https://doi.org/10.3389/fbioe.2022.804513
  73. Genes Dis. 2022 Mar;9(2): 347-357
    Ferroptosis as a novel form of regulated cell death: Implications in the pathogenesis, oncometabolism and treatment of human cancer.
    Feifei Pu, Fengxia Chen, Zhicai Zhang, Deyao Shi, Binlong Zhong, Xiao Lv, Andrew Blake Tucker, Jiaming Fan, Alexander J Li, Kevin Qin, Daniel Hu, Connie Chen, Hao Wang, Fang He, Na Ni, Linjuan Huang, Qing Liu, William Wagstaff, Hue H Luu, Rex C Haydon, Le Shen, Tong-Chuan He, Jianxiang Liu, Zengwu Shao.
      The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patient's show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment. Ferroptosis is a newly discovered iron-dependent, non-apoptotic type of cell death that is highly negatively correlated with cancer development. Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis. This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.
    Keywords:  Cancer; Cancer therapy; Clinical application; Ferroptosis; Lipid peroxidation; Pathogenesis
    DOI:  https://doi.org/10.1016/j.gendis.2020.11.019
  74. J Biomater Appl. 2022 Mar 01. 8853282211048570
    Dual functions of epigallocatechin gallate surface-modified Au nanorods@selenium composites for near-infrared-II light-responsive synergistic antibacterial therapy.
    Bingbing Wu, Yuyan Shao, Wei Zhao, Yunfang Zheng, Yunsheng Wang, Dongdong Sun.
      Diseases caused by bacterial infections pose ever-increasing threats to human health, making it important to explore alternative antibacterial strategies. Herein, epigallocatechin gallate (EGCG) surface-modified Au nanorods@selenium composites (ASE NPs) were developed for synergistic NIR-II light-responsive antibacterial therapy. In vitro antibacterial experiments demonstrated the improved antibacterial effect of ASE NPs against Staphylococcus aureus (S. aureus) compared with EGCG alone. In addition, in vivo studies demonstrated that ASE NPs cured skin wound infections and sepsis in mice caused by S. aureus. Au nanorods with excellent photothermal conversion realized synergistic photothermal therapy (PTT) in the NIR-II biowindow with an improved penetration depth at a low power density. More importantly, toxicity analysis showed that the composites had no toxic effects on major organs. Thus, the EGCG surface-modified Au nanorods@selenium composites with an NIR-II light-responsive synergistic activity hold great promise for the effective treatment of drug-resistant bacterial infections.
    Keywords:  Au nanorods; antibacterial; epigallocatechin gallate; photothermal effect; selenium
    DOI:  https://doi.org/10.1177/08853282211048570
  75. J Colloid Interface Sci. 2022 Feb 18. pii: S0021-9797(22)00293-4. [Epub ahead of print]616 304-315
    Synergistic photodynamic/photothermal bacterial inactivation over heterogeneous quaternized chitosan/silver/cobalt phosphide nanocomposites.
    Hecheng Han, Xiaoying Xu, Haopeng Kan, Yunxiang Tang, Chang Liu, Hongling Wen, Lili Wu, Yanyan Jiang, Zhou Wang, Jiurong Liu, Fenglong Wang.
      Globally, drug-resistant bacteria are a potential threat to human society owing to the overuse of antibiotics and thus, non-antibiotic bactericides are urgently needed. Herein, an innovative antibacterial nanoplatform based on quaternized chitosan (QCS)/ silver (Ag)/ cobalt phosphide (CoP) nanocomposites is envisaged for achieving near-infrared (NIR) laser-inducible rapid sterilisation. In the core-shell hybrids, Ag nanoparticles (NPs) with a size of ∼ 25 nm were uniformly deposited on CoP nanoneedles, upon which a layer of QCS (approximately 10 wt%), is coated. Numerical calculations revealed that under NIR irradiation, high-energy hot electrons arising from the surface plasmon resonance effect of Ag migrate into the interface between Ag and CoP, and amplify the photothermal effect of CoP. Meanwhile, photo-excited electrons from CoP are transported onto Ag NPs because the Schottky heterostructure facilitates the production of reactive oxygen species. Ag loading simultaneously enhances the photocatalytic and photothermal effects of CoP, achieving rapid antibacterial activity synergistically. The QCS coating improves the dispersibility of power in an aqueous system and provides contact between the antiseptics and bacteria. The ternary QCS/Ag/CoP nanocomposites achieved greater than 99.6% inactivation against S. aureus and E. coli within 10 min. In addition, the nanocomposites were confirmed to be noncytotoxic to mammals. Consequently, the QCS/Ag/CoP nanoplatforms possess great potential for rapid and effective antibacterial applications.
    Keywords:  Antibacterial activity; Photodynamic effect; Photothermal effect; Quaternized chitosan/Ag/CoP nanoplatforms; Rapid sterilization
    DOI:  https://doi.org/10.1016/j.jcis.2022.02.068
  76. J Pharm Sci. 2022 Feb 27. pii: S0022-3549(22)00082-X. [Epub ahead of print]
    Intranasal Niosomal in situ Gel as a Novel Strategy for Improving Citicoline Efficacy and Brain Delivery in Treatment of Epilepsy: In vitro and ex vivo characterization and in vivo pharmacodynamics investigation.
    Marina A Bekhet, Adel A Ali, Rasha M Kharshoum, Fatma I Abo El-Ela, Heba F Salem.
      The high hydrophilicity of citicoline and its rapid metabolism are the two main obstacles hindering intact molecules from passing the blood-brain barrier. This study aimed to formulate citicoline-loaded niosomes (CTC-NSMs) for efficient brain delivery via the intranasal route to improve management of epilepsy. CTC-NSMs were formulated via thin-film hydration method, optimized using D-optimal design, and characterized for entrapment efficiency, vesicle size, drug release, and cumulative amount permeated. The entrapment efficiency ranged from 19.44 to 61.98% with sustained drug release, and the vesicle size ranged from 125.4 to 542.5 nm with enhanced drug permeation. Cholesterol: Span ratio of 1:1.19 and cholesterol amount of 20 mg were predicted to produce optimal characteristics. Subsequently, the optimized formulation permeation confirmed a high nasal penetration using confocal laser scanning microscopy (CLSM). Afterward, the optimized CTC-NSM formulation was integrated into in situ gel to boost the residence time in the nasal cavity. Additionally, Computed Tomography (CT) was performed by labeling the optimized formulation with gold nanoparticles (GNPs) to assess brain uptake and cellular translocation after intranasal administration of CTC. Furthermore, the protection against pentylenetetrazole-induced generalized seizures and mortality were determined in rats and compared with the oral drug solution at the exact dosage. The in vivo results revealed that a low dose of CTC-NSM in situ gel had a powerful protective effect with delayed the latency for the start of convulsions. Collectively, NSM in situ gel is a potentially valuable intranasal drug delivery system that can boost the efficacy of CTC in epilepsy management.
    Keywords:  Brain computed tomography; Citicoline; Epilepsy; Niosomes; Pharmacodynamics
    DOI:  https://doi.org/10.1016/j.xphs.2022.02.012
  77. Nanoscale. 2022 Mar 04.
    Advanced metal and carbon nanostructures for medical, drug delivery and bio-imaging applications.
    Neeraj Kumar, Pankaj Chamoli, Mrinmoy Misra, M K Manoj, Ashutosh Sharma.
      Nanoparticles (NPs) offer great promise for biomedical, environmental, and clinical applications due to their several unique properties as compared to their bulk counterparts. In this review article, we overview various types of metal NPs and magnetic nanoparticles (MNPs) in monolithic form as well as embedded into polymer matrices for specific drug delivery and bio-imaging fields. The second part of this review covers important carbon nanostructures that have gained tremendous attention recently in such medical applications due to their ease of fabrication, excellent biocompatibility, and biodegradability at both cellular and molecular levels for phototherapy, radio-therapeutics, gene-delivery, and biotherapeutics. Furthermore, various applications and challenges involved in the use of NPs as biomaterials are also discussed following the future perspectives of the use of NPs in biomedicine. This review aims to contribute to the applications of different NPs in medicine and healthcare that may open up new avenues to encourage wider research opportunities across various disciplines.
    DOI:  https://doi.org/10.1039/d1nr07643d
  78. Recent Adv Drug Deliv Formul. 2022 Mar 02.
    Formulation Strategies and Therapeutic Applications of Shikonin and Related Derivatives.
    Kirandeep Kaur, Atamjit Singh, Hamayal Sharma, Sanha Punj, Neena Bedi.
      Shikonin and its derivatives are excellent representatives of biologically active naphthoquinones. A wide range of investigations carried out in the last few decades validated their pharmacological efficacy. Besides having magnificent therapeutic potential, shikonin and its derivatives suffer from various pharmacokinetic, toxicity and stability issues like poor bioavailability, nephrotoxicity, photodegradation, etc. In the recent past, various research groups have developed an extensive range of formulations to tackle these issues to ease their path to clinical practice. The latest formulation approaches have been focused on exploiting the unique features of novel functional excipients which in turn escalate the therapeutic effect of shikonin. Moreover, the codelivery approach in various drug delivery systems has taken into consideration in a recent while to reduce toxicity associated with shikonin and its derivatives. This review sheds light on the essential reports and patents published related to the array of formulations containing shikonin and its derivatives.
    Keywords:  Anticancer; Antimicrobial; Nano formulations; Patents.; Shikonin; Wound healing
    DOI:  https://doi.org/10.2174/2667387816666220302112201
  79. Braz J Biol. 2022 ;pii: S1519-69842024000100225. [Epub ahead of print]84 e255529
    Phytochemical profile and biological activities of Bromelia antiacantha extracts.
    K F Rodrigues, T C Bitencourt, J G Núñez, H O Garcia, B Buhl, G L Padilha, E M Ethur, L Hoehne, A N Bruno, E M Freitas.
      Reports from popular medicine usually act as a basis for the development of new drugs from natural compounds with therapeutic actions for serious diseases and prevalence such as cancer. Bromelia antiacantha Bertol. is a species of the Bromeliaceae family, considered an unconventional food plant, found in the south and midwest regions of Brazil. Despite the high nutritional content and pharmacological potential of its fruits, few scientific studies report its biological actions. Thus, this study evaluates the phytochemical profile of aqueous and ethanol extracts obtained from B. antiacantha fruits, as well as their possible antioxidant, antitumor, and cytotoxic activities. The aqueous extract exhibited phenolic compounds and flavonoids, while ethanol extracts indicated the presence of flavonoids and coumarin in their composition, regardless of the region of collection. The ethanolic extract demonstrated a more promising antioxidant effect than the aqueous extract and also induced a significant inhibition in the viability of human cervical cancer cells of the SiHa strain. In addition, treatment with both extracts did not alter the viability of non-tumor cells of the immortalized human keratinocyte lineage (HaCaT). These results bring new data about extracts obtained from a native plant, edible and traditionally used in popular medicine, opening new perspectives for its possible therapeutic application.
    DOI:  https://doi.org/10.1590/1519-6984.255529
  80. Pharmaceut Med. 2022 Mar 04.
    Cannabidiol and Other Phytocannabinoids as Cancer Therapeutics.
    Gerhard Nahler.
      Preclinical models provided ample evidence that cannabinoids are cytotoxic against cancer cells. Among the best studied phytocannabinoids, cannabidiol (CBD) is most promising for the treatment of cancer as it lacks the psychotomimetic properties of delta-9-tetrahydrocannabinol (THC). In vitro studies and animal experiments point to a concentration- (dose-)dependent anticancer effect. The effectiveness of pure compounds versus extracts is the subject of an ongoing debate. Actual results demonstrate that CBD-rich hemp extracts must be distinguished from THC-rich cannabis preparations. Whereas pure CBD was superior to CBD-rich extracts in most in vitro experiments, the opposite was observed for pure THC and THC-rich extracts, although exceptions were noted. The cytotoxic effects of CBD, THC and extracts seem to depend not only on the nature of cannabinoids and the presence of other phytochemicals but also largely on the nature of cell lines and test conditions. Neither CBD nor THC are universally efficacious in reducing cancer cell viability. The combination of pure cannabinoids may have advantages over single agents, although the optimal ratio seems to depend on the nature of cancer cells; the existence of a 'one size fits all' ratio is very unlikely. As cannabinoids interfere with the endocannabinoid system (ECS), a better understanding of the circadian rhythmicity of the ECS, particularly endocannabinoids and receptors, as well as of the rhythmicity of biological processes related to the growth of cancer cells, could enhance the efficacy of a therapy with cannabinoids by optimization of the timing of the administration, as has already been reported for some of the canonical chemotherapeutics. Theoretically, a CBD dose administered at noon could increase the peak of anandamide and therefore the effects triggered by this agent. Despite the abundance of preclinical articles published over the last 2 decades, well-designed controlled clinical trials on CBD in cancer are still missing. The number of observations in cancer patients, paired with the anticancer activity repeatedly reported in preclinical in vitro and in vivo studies warrants serious scientific exploration moving forward.
    DOI:  https://doi.org/10.1007/s40290-022-00420-4
  81. Recent Pat Nanotechnol. 2022 Feb 28.
    Review On Different Vesicular Drug Delivery Systems (VDDSs) And Their Applications.
    Asma M Alenzi, Sana A Albalawi, Shatha G Alghamdi, Rawan F Albalawi, Hadeel S Albalawi, Mona Qushawy.
       BACKGROUND: The vesicular drug delivery systems (VDDSs) are colloidal dispersions, which can be described as highly ordered assemblies composed of one or more concentric bilayers formed as a result of the self-assembling of amphiphilic building blocks in the presence of water.
    OBJECTIVES: VDDSs are important to target the entrapped drugs at specific sites inside the body, control the drug release, enhance the drug bioavailability, and reduce the undesired side effects.
    METHODS: There are different types of VDDSs suitable for the entrapment of both hydrophilic and lipophilic drugs. According to the composition, VDDSs are classified into lipid-based and non-lipid-based VDDSs.
    RESULTS: There are different types of VDDSs which include liposomes, ethosomes, transferosomes, ufasomes, colloidosomes, cubosomes, niosomes, bilosomes, aquasomes, etc. Conclusion: This review article aims to address the different types of VDDSs, their advantages and disadvantages, and their therapeutic applications.
    Keywords:  Bioavailability; Drug delivery; Niosomes; colloidal dispersion; drug targeting; liposomes
    DOI:  https://doi.org/10.2174/1872210516666220228150624
  82. Front Pharmacol. 2022 ;13 806470
    Dietary Polyphenols and Their Role in Oxidative Stress-Induced Human Diseases: Insights Into Protective Effects, Antioxidant Potentials and Mechanism(s) of Action.
    Mithun Rudrapal, Shubham J Khairnar, Johra Khan, Abdulaziz Bin Dukhyil, Mohammad Azam Ansari, Mohammad N Alomary, Fahad M Alshabrmi, Santwana Palai, Prashanta Kumar Deb, Rajlakshmi Devi.
      Dietary polyphenols including phenolic acids, flavonoids, catechins, tannins, lignans, stilbenes, and anthocyanidins are widely found in grains, cereals, pulses, vegetables, spices, fruits, chocolates, and beverages like fruit juices, tea, coffee and wine. In recent years, dietary polyphenols have gained significant interest among researchers due to their potential chemopreventive/protective functions in the maintenance of human health and diseases. It is believed that dietary polyphenols/flavonoids exert powerful antioxidant action for protection against reactive oxygen species (ROS)/cellular oxidative stress (OS) towards the prevention of OS-related pathological conditions or diseases. Pre-clinical and clinical evidence strongly suggest that long term consumption of diets rich in polyphenols offer protection against the development of various chronic diseases such as neurodegenerative diseases, cardiovascular diseases (CVDs), cancer, diabetes, inflammatory disorders and infectious illness. Increased intake of foods containing polyphenols (for example, quercetin, epigallocatechin-3-gallate, resveratrol, cyanidin etc.) has been claimed to reduce the extent of a majority of chronic oxidative cellular damage, DNA damage, tissue inflammations, viral/bacterial infections, and neurodegenerative diseases. It has been suggested that the antioxidant activity of dietary polyphenols plays a pivotal role in the prevention of OS-induced human diseases. In this narrative review, the biological/pharmacological significance of dietary polyphenols in the prevention of and/or protection against OS-induced major human diseases such as cancers, neurodegenerative diseases, CVDs, diabetes mellitus, cancer, inflammatory disorders and infectious diseases have been delineated. This review specifically focuses a current understanding on the dietary sources of polyphenols and their protective effects including mechanisms of action against various major human diseases.
    Keywords:  antioxidant; biomarkers; cellular signaling; dietary polyphenols; flavonoids; mechanism of action; oxidative Stress; protective function
    DOI:  https://doi.org/10.3389/fphar.2022.806470
  83. J Food Biochem. 2022 Feb 28. e14120
    Phosphatidylserine liposomes containing curcumin inhibit bone loss in osteoporotic rats: A possible synergy through a common signaling pathway.
    Alireza Partoazar, Ramin Goudarzi.
      The present study aimed to investigate the effect of phosphatidylserine liposomes containing curcumin (PSLs-Cur) on the development of osteoporosis induced by glucocorticoids (GCs) in the rat model. PSL-Cur, phosphatidylserine (PSL), curcumin (Cur), and alendronate (AL) drugs as a positive control were administrated orally to evaluate the beneficial effects of 3-week treatments on osteoporotic rats. The biochemical and biomechanical properties of bone parameters as well as gene expression were evaluated in treated rats. Moreover, histomorphometric examinations were performed on the bone tissues of the animals. The results revealed that PSL-Cur oral administration caused a significant improvement in serum markers, mechanical strength, and OPG gene expression rather than PSL or Cur administration in osteoporotic rats. Also, PSL-Cur significantly increased the thickness and volume of cortical and trabecular bone mass in comparison with the untreated osteoporotic group. The results of this study indicated that PSL-Cur had a more inhibitory effect on bone loss induced by GCs compared to AL standard drug. Our findings suggested that PSL-loaded Cur may be an appropriate alternative therapy for glucocorticoid-induced osteoporosis. PRACTICAL APPLICATIONS: Osteoporosis is one of the most serious metabolic chronic diseases that causes fragile bone due to decreased mineral density and microarchitectural deterioration in humans. The osteoprotective effects of curcumin and phosphatidylserine, as a food spice and supplementary diet, respectively, have been shown, previously. However, the low bioavailability of curcumin (Cur) due to its poor absorption, rapid metabolism, and fast systemic elimination, limits its benefits. This deficit can be modified with phosphatidylserine liposome (PSL) formulation that facilitates the gastrointestinal delivery of Cur. Moreover, PSL is known as an osteoprotective agent that may make synergy effect with Cur against GC-induced osteoporosis. In this study, daily oral administration of phosphatidylserine liposomes containing curcumin (PSL-Cur) for 3 weeks, considerably improved biochemical, biomechanical, and gene expression of bone parameters in the treated animals subjected to osteoporosis. PSL-Cur can significantly increase the thickness and volume of cortical and trabecular bone mass as well as the mechanical bone strength in animals. Experimental findings proposed PSL-Cur consumption as a proper and safe supplementary medication in the controlling of bone loss in patients with a high risk of osteoporosis.
    Keywords:  bisphosphonates; methylprednisolone; nanoliposome; nutrition; synergy
    DOI:  https://doi.org/10.1111/jfbc.14120
  84. FEBS J. 2022 03;289(5): 1156-1159
    Cancer epigenetics: promises and pitfalls for cancer therapy.
    Eleni Skourti, Paraminder Dhillon.
      Over the past few decades, epigenetic regulators have emerged as major players in cellular processes that drive cancer initiation and progression, and subsequently modulate the responsiveness of cancers to therapeutic agents. This Special Issue of The FEBS Journal, Cancer Epigenetics, features an exciting collection of review articles that focus on the functions of a broad spectrum of epigenetic modulators in cancer. The diverse topics explored herein range from the roles of transposable elements and chromatin architecture in cancer and the most recent research advances on cancer-associated histone variants (oncohistones), to the effects of altered epigenetics on transcription and advanced cancer cell phenotypes. Moreover, the prospective key function of cancer metabolism in linking epigenetics and transcriptional regulation, and the potential of epigenetics for targeted cancer therapeutics is discussed. We hope that this collection of articles will give readers an enlightening overview of the most recent advances in the fast-moving field of cancer epigenetics.
    Keywords:  DNA methylation; cancer epigenetics; chromatin; histone modifications; transcriptional regulation
    DOI:  https://doi.org/10.1111/febs.16395
  85. Int J Pharm. 2022 Feb 25. pii: S0378-5173(22)00159-4. [Epub ahead of print] 121605
    The science of resveratrol, formulation, pharmacokinetic barriers and its chemotherapeutic potential.
    Imogen Robertson, Tung Wai Hau, Farheen Sami, Md Sajid Ali, Vishal Badgujar, Sheikh Murtuja, M Saquib Hasnain, Abdullah Khan, Shahnaz Majeed, Mohammed Tahir Ansari.
      Chemopreventive properties of resveratrol has been studied for decades. Despite its potential for chemotherapeutic advancement, the compound has pharmaceutical limitations, such as, the drug has a poor pharmacokinetic profile and low bioavailability. Studies have comforting results that that the nano-formulations may aid the future resveratrol drug development. Resveratrol can also be encapsulated as co-drug with an anticipation of gaining improved targeting and pharmacokinetic parameters, as well as achieving desired therapeutic plasma levels. It has been envisaged that the nanoformulations can also address the issue of drug accumulation, which may lead to hepatotoxicity. Nanoformulations can bring a major improvement in the bioavailability of resveratrol but still the formulation still suffers with pharmacokinetics issues clinically. This review encompasses the pharmacokinetics barriers associated with resveratrol and a possible suggestion to overcome those barriers for improving absorbance, reducing toxicity andimproving the drug releaseand encapsulation efficiency. The article also suggest that co-administration of resveratrol with chemotherapeutic drugsmust be tested in vivo on a wide range of cancers to avoid accidental proliferation exacerbation. The review's focusses on the resveratrol formulation and make suggestions for improvements in order to overcome the pharmacokinetic and toxicity issues.
    Keywords:  Lipid nanoformulations; Pharmacokinetics of resveratrol; Resveratrol
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.121605
  86. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2022 Feb 28. e1786
    Enzyme-mediated intratumoral self-assembly of nanotheranostics for enhanced imaging and tumor therapy.
    Yue Yuan, Jeff W M Bulte.
      Enzyme-mediated intratumoral self-assembled (EMISA) nanotheranostics represent a new class of smart agents for combined imaging and therapy of cancer. Cancer cells overexpress various enzymes that are essential for high metabolism, fast proliferation, and tissue invasion and metastasis. By conjugating small molecules that contain an enzyme-specific cleavage site to appropriate chemical linkers, it is possible to induce self-assembly of nanostructures in tumor cells having the target enzyme. This approach of injecting small theranostic molecules that eventually become larger nanotheranostics in situ avoids some of the major limitations that are encountered when injecting larger, pre-assembled nanotheranostics. The advantage of EMISA nanotheranostics include the avoidance of nonspecific uptake and rapid clearance by phagocytic cells, increased cellular accumulation, reduced drug efflux and prolonged cellular exposure time, all of which lead to an amplified imaging signal and therapeutic efficacy. We review here the different approaches that can be used for preparing EMISA-based organic, inorganic, or organic/inorganic hybrid nanotheranostics based on noncovalent interactions and/or covalent bonding. Imaging examples are shown for fluorescence imaging, nuclear imaging, photoacoustic imaging, Raman imaging, computed tomography imaging, bioluminescent imaging, and magnetic resonance imaging. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Biology-Inspired Nanomaterials > Peptide-Based Structures.
    Keywords:  enzyme; intratumoral; nanotheranostics; self-assembly
    DOI:  https://doi.org/10.1002/wnan.1786
  87. 3 Biotech. 2022 Mar;12(3): 70
    Nano to rescue: repository of nanocarriers for targeted drug delivery to curb breast cancer.
    Poonam Banthia, Lokesh Gambhir, Asha Sharma, Dhiraj Daga, Neha Kapoor, Rishabh Chaudhary, Gaurav Sharma.
      Breast cancer is a heterogeneous disease with different intrinsic subtypes. The conventional treatment of surgical resection, chemotherapy, immunotherapy and radiotherapy has not shown significant improvement in the survival rate of breast cancer patients. The therapeutics used cause bystander toxicities deteriorating healthy tissues. The breakthroughs of nanotechnology have been a promising feat in selective targeting of tumor site thus increasing the therapeutic gain. By the application of nanoenabled carriers, nanomedicines ensure targeted delivery, stability, enhanced cellular uptake, biocompatibility and higher apoptotic efficacy. The present review focuses on breakthrough of nanoscale intervention in targeted drug delivery as novel class of therapeutics. Nanoenabled carriers like polymeric and metallic nanoparticles, dendrimers, quantum dots, liposomes, solid lipid nanoparticles, carbon nanotubes, drug-antibody conjugates and exosomes revolutionized the targeted therapeutic delivery approach. These nanoassemblies have shown additional effect of improving the solubility of drugs such as paclitaxel, reducing the dose and toxicity. The present review provides an insight on the different drug conjugates employed/investigated to curb breast cancer using nanocarrier mediated targeted drug delivery. However, identification of appropriate biomarkers to target, clearer insight of the biological processes, batch uniformity, reproducibility, nanomaterial toxicity and stabilities are the hurdles faced by nanodrugs. The potential of nano-therapeutics delivery necessitates the agglomerated efforts of research community to bridge the route of nanodrugs for scale-up, commercialization and clinical applications.
    Keywords:  Breast cancer; Drug delivery; Nanocarriers; Nanomaterials; Nanomedicine
    DOI:  https://doi.org/10.1007/s13205-022-03121-6
  88. Drug Discov Today. 2022 Feb 24. pii: S1359-6446(22)00072-1. [Epub ahead of print]
    Stimuli-sensitive drug delivery systems for site-specific antibiotic release.
    Faiqa Nazir, Tanveer A Tabish, Fatima Tariq, Shanza Iftikhar, Rijja Wasim, Gul Shahnaz.
      Site-specific delivery of antibiotics has always been a high-priority area in pharmaceutical research. Conventionally used antibiotics suffer several limitations, such as low accumulation and penetration in diseased cells/tissues, limited bioavailability of drugs, drug resistance, and off-target toxicity. To overcome these limitations, several strategies have been exploited for delivering antibiotics to the site of infection, such as the use of stimuli-responsive antibiotic delivery systems, which can release antibiotics in a controlled and timely fashion. These stimuli can either be exogenous (light, magnetism, ultrasound, and electrical) or endogenous (pH, redox reactions, and enzymatic). In this review, we present a summary of recent developments in the field of stimuli-based targeted drug delivery systems for the site-specific release of antibiotics.
    Keywords:  Antibiotic release; External stimuli-responsive drug delivery; Internal stimuli-responsive drug delivery; Nanoparticles; Targeted drug delivery
    DOI:  https://doi.org/10.1016/j.drudis.2022.02.014
  89. Cancer Control. 2022 Jan-Dec;29:29 10732748221075468
    Glucose Influences the Response of Glioblastoma Cells to Temozolomide and Dexamethasone.
    Anna M Bielecka-Wajdman, Tomasz Ludyga, Daria Smyk, Wojciech Smyk, Magdalena Mularska, Patrycja Świderek, Wojciech Majewski, Christina Susanne Mullins, Michael Linnebacher, Ewa Obuchowicz.
       OBJECTIVE: Current research indicates that weakness of glucose metabolism plays an important role in silencing of invasiveness and growth of hypoxic tumors such as GBM. Moreover, there are indications that DXM, frequently used in treatment, may support GBM energy metabolism and provoke its recurrence.
    METHODS: We carried out in vitro experiments on the commercial T98G cell line and two primary GBM lines (HROG02, HROG17) treated with TMZ and/or DXM in physiological oxygen conditions for GBM (2.5% oxygen) and for comparison, in standard laboratory conditions (20% oxygen). The influence of different glucose levels on selected malignancy features of GBM cells-cellular viability and division, dynamic of cell culture changes, colony formation and concentration of InsR have been elevated.
    RESULTS: Under 2.5% oxygen and high glucose concentration, an attenuated cytotoxic effect of TMZ and intensification of malignancy features in all glioblastoma cell lines exposed to DXM was seen. Furthermore, preliminary retrospective analysis to assess the correlation between serum glucose levels and Ki-67 expression in surgical specimens derived from patients with GBM (IV) treated with radio-chemotherapy and prophylactic DXM therapy was performed.
    CONCLUSION: The data suggest a link between the in vitro study results and clinical data. High glucose can influence on GBM progression through the promotion of the following parameters: cell viability, dispersal, InsR expression and cell proliferation (Ki-67). However, this problem needs more studies and explain the mechanism of action studied drugs.
    Keywords:  adjuvant treatment in brain cancer; brain tumor; chemotherapy in brain cancer; glioblastoma; glucose in cancer
    DOI:  https://doi.org/10.1177/10732748221075468
  90. J Food Biochem. 2022 Mar 04. e14077
    Cinnamon could improve hepatic steatosis caused by a high-fat diet via enhancing hepatic beta-oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation in male rats.
    Baicheng Li, Jia Li, Shuwen Hu.
      Obesity is a health and medical problem and is known as the accumulation of fat that increases the risk of cardiovascular, type 2 diabetes mellitus, and infertility. Cinnamon is a spice that is used mainly as a flavoring additive and folk remedies to treat diabetes. Molecular mechanisms of its effects on hepatic lipogenesis and beta-oxidation, inflammation, and oxidative damage are not fully understood. Therefore, the aim of this study was to evaluate the protective and therapeutic effect of different doses of cinnamon in obese male rats. Forty-eight adult male Wister rats were randomly assigned into eight controlled and treated groups. Serum levels of lipid, glucose, and insulin profiles were measured along with liver levels of antioxidant enzymes, MDA and TNF-α. Hepatic expression of genes involved in beta-oxidation, lipogenesis, oxidative stress, and inflammation was also evaluated. Hepatic levels of oxidative and inflammatory biomarkers and serum levels of glucose, liver enzymes, insulin, and lipid profiles increased significantly in obese rats. Moreover, hepatic expression of SREBP-1c and NF-κB increased, and PPAR-alpha, CD36, FAS, CPT-1, and Nrf-2 decreased in obese rats. However, pretreatment and treatment with different doses of cinnamon in obese rats could significantly ameliorate them in obese rats. It can be concluded that cinnamon could improve hepatic steatosis caused by a high-fat diet via enhancing hepatic beta-oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation in male rats. PRACTICAL APPLICATIONS: Obesity as a medical and psychiatric problem is seen in more than a third of the world's population. Obesity leads to cardiovascular disease, diabetes, and in some cases even death. Cinnamon as a spice and folk remedy has long been used as a treatment for obesity and liver disease. Cinnamon has received a great of attention from the past to the present due to its pharmacological properties and in addition to its availability, cheapness and low side effects. Cinnamon can prevent dyslipidemia, hyperglycemia, oxidative damage, and inflammation by modulating multiple signaling pathways. Our results showed that cinnamon could improve hepatic steatosis caused by HFD via enhancing hepatic beta-oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation. Therefore, it can be recommended that cinnamon and its products can be used as a very suitable option for the production of pharmaceutical supplements for the prevention and treatment of metabolic diseases.
    Keywords:  beta-oxidation; cinnamon; inflammation; lipogenesis; obesity
    DOI:  https://doi.org/10.1111/jfbc.14077
  91. Med Sci (Basel). 2022 Feb 18. pii: 15. [Epub ahead of print]10(1):
    Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.
    Hisham F Bahmad, Timothy Demus, Maya M Moubarak, Darine Daher, Juan Carlos Alvarez Moreno, Francesca Polit, Olga Lopez, Ali Merhe, Wassim Abou-Kheir, Alan M Nieder, Robert Poppiti, Yumna Omarzai.
      Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials.
    Keywords:  CRPC; androgen-deprivation therapy; drug repurposing; prostate cancer
    DOI:  https://doi.org/10.3390/medsci10010015
  92. Int J Nanomedicine. 2022 ;17 837-854
    Hybrid Cell Membrane-Functionalized Biomimetic Nanoparticles for Targeted Therapy of Osteosarcoma.
    Jia-Xin Cai, Ji-Hua Liu, Jun-Yong Wu, Yong-Jiang Li, Xiao-Han Qiu, Wen-Jie Xu, Ping Xu, Da-Xiong Xiang.
       Purpose: In order to prepare a biomimetic nano-carrier which has inflammatory chemotaxis, homologous targeting and reduce immune clearance, for targeted chemotherapy of osteosarcoma, we fabricated the paclitaxel-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with 143B-RAW hybrid membrane (PTX-PLGA@[143B-RAW] NPs) and evaluate its anti-cancer efficacy in vitro and vivo.
    Methods: PTX-PLGA@[143B-RAW] NPs were prepared by the ultrasonic method and were characterized by size, zeta potential, polymer dispersion index (PDI), Coomassie bright blue staining, transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC). Cellular uptake, cell viability assay, flow cytometry and chemotactic effect of PTX-PLGA@[143B-RAW] NPs were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy and safety of PTX-PLGA@[143B-RAW] NPs were evaluated in 143B osteosarcoma xenograft mice.
    Results: The hybrid membrane successfully coated onto the surface of PLGA nanoparticles. PTX-PLGA@[143B-RAW] NPs had a drug loading capacity of 4.24 ± 0.02% and showed targeting ability to osteosarcoma. PTX-PLGA@[143B-RAW] NPs showed high cellular uptake and improved anti-cancer efficacy against 143B cells. More importantly, PTX-PLGA@[143B-RAW] NPs treatment suppressed tumor growth in tumor-bearing mice with minimal damage to normal tissues.
    Conclusion: PTX-PLGA@[143B-RAW] NPs could be used for targeted drug delivery and osteosarcoma therapy.
    Keywords:  biomimetic nano-drug delivery system; osteosarcoma; paclitaxel; targeted therapy
    DOI:  https://doi.org/10.2147/IJN.S346685
  93. J Bone Miner Res. 2022 Feb 27.
    Distinct roles of glutamine metabolism in benign and malignant cartilage tumors with IDH mutations.
    Hongyuan Zhang, Vijitha Puviindran, Puviindran Nadesan, Xiruo Ding, Leyao Shen, Yuning J Tang, Hidetoshi Tsushima, Yasuhito Yahara, Ga I Ban, Guo-Fang Zhang, Courtney M Karner, Benjamin Alman.
      Enchondromas and chondrosarcomas are common cartilage neoplasms that are either benign or malignant respectively. The majority of these tumors harbor mutations in either IDH1 or IDH2. Glutamine metabolism has been implicated as a critical regulator of tumors with IDH mutations. Using genetic and pharmacological approaches, we demonstrated that glutaminase-mediated glutamine metabolism played distinct roles in enchondromas and chondrosarcomas with IDH1 or IDH2 mutations. Glutamine affected cell differentiation and viability in these tumors differently through different downstream metabolites. During murine enchondroma-like lesion development, glutamine-derived α-ketoglutarate promoted hypertrophic chondrocyte differentiation and regulated chondrocyte proliferation. Deletion of glutaminase in chondrocytes with Idh1 mutation increased the number and size of enchondroma-like lesions. In contrast, pharmacological inhibition of glutaminase in chondrosarcoma xenografts reduced overall tumor burden partially because glutamine-derived non-essential amino acids played an important role in preventing cell apoptosis. This study demonstrates that glutamine metabolism plays different roles in tumor initiation and cancer maintenance. Supplementation of α-ketoglutarate and inhibiting GLS may provide a therapeutic approach to suppress enchondroma and chondrosarcoma tumor growth respectively.
    Keywords:  CARTILAGE TUMORS; CHONDROCYTE DIFFERENTIATION; GLUTAMINE METABOLISM; GROWTH PLATE; ISOCITRATE DEHYDROGENASE
    DOI:  https://doi.org/10.1002/jbmr.4532
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