bims-kracam 2022-11-27 papers

on K-Ras in cancer metabolism

Issue of 2022–11–27
forty-four papers selected by
Yasmin Elkabani, Egyptian Foundation for Research and Community Development

Recent advances in understanding the metabolic plasticity of ovarian cancer: A systematic review.
Neutrophil mediated drug delivery for targeted glioblastoma therapy: A comprehensive review.
Targeting Oncogenic Rewiring of Lipid Metabolism for Glioblastoma Treatment.
5-Aminolevulinic Acid-Mediated Photodynamic Therapy Potentiates the Effectiveness of Doxorubicin in Ewing Sarcomas.
The therapeutic potential of natural products for treating pancreatic cancer.
Recent Photosensitizer Developments, Delivery Strategies and Combination-based Approaches for Photodynamic Therapy.
Levothyroxine: Conventional and novel drug delivery formulations.
Progress in research on the role of amino acid metabolic reprogramming in tumour therapy: A review.
Curcumin: An epigenetic regulator and its application in cancer.
Osmotic Pump Drug Delivery Systems-A Comprehensive Review.
Regulation of Cholesterol Metabolism by Phytochemicals Derived from Algae and Edible Mushrooms in Non-Alcoholic Fatty Liver Disease.
An Overview of Antitumour Activity of Polysaccharides.
Injectable rapidly dissolving needle-type gelatin implant capable of delivering high concentrations of H2O2 through intratumoral injection.
Can Natural Products Targeting EMT Serve as the Future Anticancer Therapeutics?
Biodegradable PEG-PCL Nanoparticles for Co-delivery of MUC1 Inhibitor and Doxorubicin for the Confinement of Triple-Negative Breast Cancer.
Co-encapsulation of paclitaxel and 5-fluorouracil in folic acid-modified, lipid-encapsulated hollow mesoporous silica nanoparticles for synergistic breast cancer treatment.
Layer-by-layer development of chitosan/alginate-based platelet-mimicking nanocapsules for augmenting doxorubicin cytotoxicity against breast cancer.
Curcumin-Loaded Chitosan Nanoparticle Preparation and Its Protective Effect on Celecoxib-induced Toxicity in Rat isolated Cardiomyocytes and Mitochondria.
Targeting hypoxia-related metabolism molecules: How to improve tumour immune and clinical treatment?
Efficacy of Diclofenac Transdermal Patch in Therapeutic Extractions: A Literature Review.
Recent Updates on Source, Biosynthesis, and Therapeutic Potential of Natural Flavonoid Luteolin: A Review.
Editorial: Nanotechnology for natural products.
NF-κB inhibitors gifted by nature: The anticancer promise of polyphenol compounds.
Nutritional Epigenetics and Phytochemicals in Cancer Formation.
Anti-inflammatory and anti-allergic potential of dietary flavonoids: A review.
Recent Advances in Nanomaterials for Asthma Treatment.
Amino Acids in Cancer and Cachexia: An Integrated View.
Preparation of 6-Mercaptopurine Loaded Liposomal Formulation for Enhanced Cytotoxic Response in Cancer Cells.
Natural Reno-Protective Agents against Cyclosporine A-Induced Nephrotoxicity: An Overview.
Quercetin Loaded Cationic Solid Lipid Nanoparticles in a Mucoadhesive In Situ Gel-A Novel Intravesical Therapy Tackling Bladder Cancer.
Ferroptosis in lymphoma: Emerging mechanisms and a novel therapeutic approach.
Engineered nanoparticles as emerging gene/drug delivery systems targeting the nuclear factor-κB protein and related signaling pathways in cancer.
Formulation considerations for improving intranasal delivery of CNS acting therapeutics.
Biologically inspired stealth - camouflaged strategies in nanotechnology for the improved therapies in various diseases.
Ferroptosis: A new therapeutic target for bladder cancer.
Developments on the Smart Hydrogel-Based Drug Delivery System for Oral Tumor Therapy.
Ginger Extract-Loaded Sesame Oil-Based Niosomal Emulgel: Quality by Design to Ameliorate Anti-Inflammatory Activity.
Liposomes and liposome-like nanoparticles: From anti-fungal infection to the COVID-19 pandemic treatment.
Caffeine-loaded nano/micro-carriers: Techniques, bioavailability, and applications.
Enzymatic lipophilization of bioactive compounds with high antioxidant activity: a review.
The anti-cancer effect of chitosan/resveratrol polymeric nanocomplex against triple-negative breast cancer; an in vitro assessment.
Naringin's Prooxidant Effect on Tumor Cells: Copper's Role and Therapeutic Implications.
Editorial: Sphingolipid metabolism and cancer.
The application of antidepressant drugs in cancer treatment.

Heliyon. 2022 Nov;8(11): e11487

Recent advances in understanding the metabolic plasticity of ovarian cancer: A systematic review.

Hiroshi Kobayashi.

  Epithelial ovarian cancer (EOC) is a gynecologic malignancy with a poor prognosis due to resistance to first-line chemotherapeutic agents. Some cancer cells are primarily dependent on glycolysis, but others favor mitochondrial oxidative phosphorylation (OXPHOS) over glycolysis. Changes in metabolic reprogramming have been reported to be involved in cancer cell survival. In this review, we summarize the metabolic profiles (e.g., metabolic heterogeneity, plasticity, and reprogramming) and adaptation to the dynamic tumor microenvironment and discuss potential novel therapeutic strategies. A literature search was performed between January 2000 and March 2022 in the PubMed and Google Scholar databases using a combination of specific terms. Ovarian cancer cells, including cancer stem cells, depend on glycolysis, OXPHOS, or both for survival. Several environmental stresses, such as nutrient starvation or glucose deprivation, hypoxic stress, acidification, and excessive reactive oxygen species (ROS) generation, reprogram the metabolic pathways to adapt. The interaction between tumors and adjacent stromal cells allows cancer cells to enhance mitochondrial energy metabolism. The metabolic reprogramming varies depending on genomic and epigenetic alterations of metabolism-related genes and the metabolic environment. Developing accurate and non-invasive methods for early identification of metabolic alterations could facilitate optimal cancer diagnosis and treatment. Cancer metabolism research has entered an exciting era where novel strategies targeting metabolic profiling will become more innovative.

Keywords:  Glycolysis; Metabolic plasticity; Metabolic reprogramming; Ovarian cancer; Oxidative phosphorylation; Stem cells; Warburg effect

DOI:  https://doi.org/10.1016/j.heliyon.2022.e11487
Biomed Pharmacother. 2022 Dec;pii: S0753-3322(22)01230-6. [Epub ahead of print]156 113841

Neutrophil mediated drug delivery for targeted glioblastoma therapy: A comprehensive review.

Hamed Hosseinalizadeh, Mehrdad Mahmoodpour, Zahra Razaghi Bahabadi, Michael R Hamblin, Hamed Mirzaei.

  Glioblastoma is the most common brain cancer in adults and presents a major challenge for targeted drug delivery due to the blood-brain barrier (BBB) and the highly infiltrative growth of the glioma cells into the brain. Cell-mediated drug-delivery systems have been proposed as a potential strategy to enhance the effects of drugs and reduce their side effects in the treatment of cancer. Neutrophils are the most abundant type of WBC in humans and can overcome impermeable barriers and transport drugs into inflamed sites such as tumors. Therefore, a promising approach for an innovative drug delivery system is the use of neutrophils as Trojan horses for drug delivery. However, compared to other leukocytes such as macrophages, little is known about how human neutrophils respond to and take up synthetic particles. In this review, we summarize the factors affecting the uptake of nanoparticles (NPs) by neutrophils, as well as recent advances and challenges related to the interaction between neutrophils and NPs, with particular emphasis on the interaction of magnetic mesoporous silica NPs, liposomes, albumin NPs, and PLGA NPs with neutrophils. Finally, the potential application of neutrophil-based drug delivery systems for the prevention of glioblastoma recurrence and also the potential application of neutrophil-mimicking nanoparticles (NM-NPs) in glioblastoma therapy are discussed.

Keywords:  Glioma; Inflammation; Nanoparticles; Neutrophils; Targeted drug delivery

DOI:  https://doi.org/10.1016/j.biopha.2022.113841
Int J Mol Sci. 2022 Nov 10. pii: 13818. [Epub ahead of print]23(22):

Targeting Oncogenic Rewiring of Lipid Metabolism for Glioblastoma Treatment.

Haksoo Lee, Dahye Kim, BuHyun Youn.

  Glioblastoma (GBM) is the most malignant primary brain tumor. Despite increasing research on GBM treatment, the overall survival rate has not significantly improved over the last two decades. Although recent studies have focused on aberrant metabolism in GBM, there have been few advances in clinical application. Thus, it is important to understand the systemic metabolism to eradicate GBM. Together with the Warburg effect, lipid metabolism has emerged as necessary for GBM progression. GBM cells utilize lipid metabolism to acquire energy, membrane components, and signaling molecules for proliferation, survival, and response to the tumor microenvironment. In this review, we discuss fundamental cholesterol, fatty acid, and sphingolipid metabolism in the brain and the distinct metabolic alterations in GBM. In addition, we summarize various studies on the regulation of factors involved in lipid metabolism in GBM therapy. Focusing on the rewiring of lipid metabolism will be an alternative and effective therapeutic strategy for GBM treatment.

Keywords:  cholesterol; fatty acid; glioblastoma; lipid metabolism; metabolic reprogramming; sphingolipid

DOI:  https://doi.org/10.3390/ijms232213818
Biomedicines. 2022 Nov 11. pii: 2900. [Epub ahead of print]10(11):

5-Aminolevulinic Acid-Mediated Photodynamic Therapy Potentiates the Effectiveness of Doxorubicin in Ewing Sarcomas.

Lea Marocco, Felix Umrath, Saskia Sachsenmaier, Robert Rabiner, Nikolaus Wülker, Marina Danalache.

  Ewing sarcomas (ES) are aggressive primary bone tumors that require radical therapy. Promising low toxicity, 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) could enhance the effectiveness of conventional treatment modalities (e.g., doxorubicin (DOX)), improving, thus, the anti-tumorigenic effects. In this study, we investigated the effects of DOX and 5-ALA PDT alone or in combination on three different human ES cell lines. Cell viability, reactive oxygen species (ROS) production, and cellular stiffness were measured 24 h after PDT (blue light-wavelength 436 nm with 5-ALA) with or without DOX. ES cell lines have a different sensitivity to the same doses and exposure of 5-ALA PDT. DOX in combination with 5-ALA PDT was found to be effective in impairing the viability of all ES cells while also increasing cytotoxic activity by high ROS production. The stiffness of the ES cells increased significantly (p < 0.05) post treatment. Overall, our results showed that across multiple ES cell lines, 5-ALA PDT can successfully and safely be combined with DOX to potentiate the therapeutic effect. The 5-ALA PDT has the potential to be a highly effective treatment when used alone or in conjunction with other treatments. More research is needed to assess the effectiveness of 5-ALA PDT in in vivo settings.

Keywords:  Ewing sarcoma; atomic force microscopy; combination therapy; cytoskeleton; doxorubicin; photodynamic therapy

DOI:  https://doi.org/10.3390/biomedicines10112900
Front Pharmacol. 2022 ;13 1051952

The therapeutic potential of natural products for treating pancreatic cancer.

Xia He, Ning Wang, Yu Zhang, Xiaobo Huang, Yi Wang.

  Pancreatic cancer is one of the most malignant tumors of the digestive tract, with the poor prognosis and low 5-year survival rate less than 10%. Although surgical resection and chemotherapy as gemcitabine (first-line treatment) has been applied to the pancreatic cancer patients, the overall survival rates of pancreatic cancer are quite low due to drug resistance. Therefore, it is of urgent need to develop alternative strategies for its treatment. In this review, we summarized the major herbal drugs and metabolites, including curcumin, triptolide, Panax Notoginseng Saponins and their metabolites etc. These compounds with antioxidant, anti-angiogenic and anti-metastatic activities can inhibit the progression and metastasis of pancreatic cancer. Expecting to provide comprehensive information of potential natural products, our review provides valuable information and strategies for pancreatic cancer treatment.

Keywords:  curcumin; natural products; panax notoginseng saponins; pancreatic cancer; toosendanin; triptolide

DOI:  https://doi.org/10.3389/fphar.2022.1051952
Photochem Photobiol. 2022 Nov 26.

Recent Photosensitizer Developments, Delivery Strategies and Combination-based Approaches for Photodynamic Therapy.

Nory Mariño-Ocampo, Luciano Dibona-Villanueva, Elizabeth Escobar Álvarez, Daniel Guerra-Díaz, Daniel Zúñiga-Núñez, Denis Fuentealba, José Robinson-Duggon.

Photodynamic therapy of cancer (PDT) is a therapeutic technique, minimally invasive, which is currently used to treat cancerous lesions and tumors that has been in the spotlight for its potential over the recent decades. Nonetheless, PDT still needs further development to become a first option treatment for patients. This review compiles recent progress in several aspects of the current research in the constantly growing area of PDT to overcome the main challenges as an attempt to serve as a guide and reference for newcomers into this research area. This review has been prepared to highlight the use of chemical modifications on photosensitizers to improve their solubility, photostability, selectivity and phototoxicity. Additionally, the use of liposomes and cavitands as drug delivery systems to aid in the biodistribution and bioaccumulation of photosensitizers are presented. Also, the combination of PDT with chemotherapy or immunotherapy as an option to boost and improve treatment outcomes are discussed. Finally, the inhibition of antioxidant enzymes as a strategy for a synergistic effect to ameliorate the performance of the photosensitizers in PDT are presented as an alternative for future researchers.

DOI: https://doi.org/10.1111/php.13749
Endocr Rev. 2022 Nov 22. pii: bnac030. [Epub ahead of print]

Levothyroxine: Conventional and novel drug delivery formulations.

Hanqing Liu, Wei Li, Wen Zhang, Shengrong Sun, Chuang Chen.

  Despite the fact that levothyroxine is one of the most prescribed medications in the world, its bioavailability has been reported to be impaired by many factors, including interfering drugs or foods and concomitant diseases, and persistent hypothyroidism with a high dose of levothyroxine is thus elicited. Persistent hypothyroidism can also be induced by noninterchangeability between formulations and poor compliance. To address these issues, some strategies have been developed. Novel formulations (liquid solutions and soft-gel capsules) have been designed to eliminate malabsorption. Some other delivery routes (injections, suppositories, sprays, and sublingual and transdermal administrations) are aimed at circumventing different difficulties in dosing, such as thyroid emergencies and dysphagia. Moreover, nanomaterials have been used to develop delivery systems for the sustained release of levothyroxine to improve patient compliance and reduce costs. Some delivery systems encapsulating nanoparticles show promising release profiles. In this review, we first summarize the medical conditions that interfere with the bioavailability of oral levothyroxine and discuss the underlying mechanisms and treatments. The efficacy of liquid solutions and soft-gel capsules are systematically evaluated. We further summarize the novel delivery routes for levothyroxine and their possible applications. Nanomaterials in the levothyroxine field are then discussed and compared based on their load and release profile. We hope the article provides novel insights into the drug delivery of levothyroxine.

Keywords:  LT4; injection; liquid solution; malabsorption; nanoparticle; soft gel capsule

DOI:  https://doi.org/10.1210/endrev/bnac030
Biomed Pharmacother. 2022 Dec;pii: S0753-3322(22)01312-9. [Epub ahead of print]156 113923

Progress in research on the role of amino acid metabolic reprogramming in tumour therapy: A review.

Dong Wang, Xin Wan.

  Malignant tumors are non-communicable diseases that affect human life health and quality of life. Anti-tumour-related research has also been the focus and difficulty in oncology research. With the rise of metabolomics, tumour biology, and the theory of tumour reprogramming, amino acid metabolic reprogramming has become a new target for antitumor research. Amino acids provide biomolecules such as nucleotides for tumour cell proliferation, invasion, and immune escape processes. They are also essential metabolites for immune cell activation and antitumor effects in the tumour microenvironment. Abnormal changes in amino acid metabolism are closely related to tumour development and immunity. Some essential proteins or critical enzymes in their metabolic pathways can be used for tumour diagnosis and prognosis assessment markers. Therefore, this paper reviews the effects of amino acid metabolism on tumour cell proliferation and the abnormal alterations of amino acid metabolism during the tumour metabolic cycle and analyzes and prospects the tumour therapeutic drugs targeting amino acid metabolism. This paper provides theoretical references for the in-depth study of the regulation of amino acid metabolism on tumour development and its possible therapeutic targets.

Keywords:  Amino acids; Metabolic reprogramming; Targeted amino acid metabolism; Tumour immunity; Tumour therapy

DOI:  https://doi.org/10.1016/j.biopha.2022.113923
Biomed Pharmacother. 2022 Dec;pii: S0753-3322(22)01345-2. [Epub ahead of print]156 113956

Curcumin: An epigenetic regulator and its application in cancer.

Tianqi Ming, Qiu Tao, Shun Tang, Hui Zhao, Han Yang, Maolun Liu, Shan Ren, Haibo Xu.

  Nowadays, one of the leading causes of death in humans is cancer, which is still on the rise globally and is in great need of intense study on the pathogenic mechanism and effective therapy. Epigenetics is a discipline that studies heritable changes in gene expression without alteration of DNA sequence. Epigenetic changes mainly involve DNA methylation, histone modifications and non-coding RNA (ncRNA) expression, which are interconnected to play a crucial role in the initiation and progression of various malignancies. Curcumin is a type of plant-derived polyphenolic compound with strong bioactivity against various disorders, particularly cancer. Retrieving commonly used databases such as PubMed, Google Scholar and CNKI, we summarized recent advances in the efficacy of curcumin on cancer and its epigenetic regulation in terms of DNA methylation, histone modifications and ncRNA expression. Furthermore, we also focused on improving the bioavailability of curcumin by development of novel curcumin analogs with high bioavailability, nanoparticles-loaded drug delivery system for curcumin, and combination therapy of curcumin with other agents. This review provides comprehensive insights into the molecular mechanisms, on the basis of epigenetic regulation, underlying the clinical application of curcumin in cancer.

Keywords:  Bioavailability; Cancer; Curcumin; Epigenetics

DOI:  https://doi.org/10.1016/j.biopha.2022.113956
Pharmaceuticals (Basel). 2022 Nov 18. pii: 1430. [Epub ahead of print]15(11):

Osmotic Pump Drug Delivery Systems-A Comprehensive Review.

Yosif Almoshari.

  In the last couple of years, novel drug delivery systems (NDDS) have attracted much attention in the food and pharmaceutical industries. NDDS is a broad term that encompasses many dosage forms, one of which is osmotic pumps. Osmotic pumps are considered to be the most reliable source of controlled drug delivery, both in humans and in animals. These pumps are osmotically controlled and release active agents through osmotic pressure. To a large extent, drug release from such a system is independent of gastric fluids. Based on such unique properties and advantages, osmotic pumps have made their mark on the pharmaceutical industry. This review summarizes the available osmotic devices for implantation and osmotic tablets for oral administration.

Keywords:  controlled release system; novel drug delivery system; osmosis; osmotic pressure; osmotic pump

DOI:  https://doi.org/10.3390/ph15111430
Int J Mol Sci. 2022 Nov 08. pii: 13667. [Epub ahead of print]23(22):

Regulation of Cholesterol Metabolism by Phytochemicals Derived from Algae and Edible Mushrooms in Non-Alcoholic Fatty Liver Disease.

Yahav Eilam, Noam Pintel, Hamdan Khattib, Natalie Shagug, Raged Taha, Dorit Avni.

  Cholesterol synthesis occurs in almost all cells, but mainly in hepatocytes in the liver. Cholesterol is garnering increasing attention for its central role in various metabolic diseases. In addition, cholesterol is one of the most essential elements for cells as both a structural source and a player participating in various metabolic pathways. Accurate regulation of cholesterol is necessary for the proper metabolism of fats in the body. Disturbances in cholesterol homeostasis have been linked to various metabolic diseases, such as hyperlipidemia and non-alcoholic fatty liver disease (NAFLD). For many years, the use of synthetic chemical drugs has been effective against many health conditions. Furthermore, from ancient to modern times, various plant-based drugs have been considered local medicines, playing important roles in human health. Phytochemicals are bioactive natural compounds that are derived from medicinal plants, fruit, vegetables, roots, leaves, and flowers and are used to treat a variety of diseases. They include flavonoids, carotenoids, polyphenols, polysaccharides, vitamins, and more. Many of these compounds have been proven to have antioxidant, anti-inflammatory, antiobesity and antihypercholesteremic activity. The multifaceted role of phytochemicals may provide health benefits to humans with regard to the treatment and control of cholesterol metabolism and the diseases associated with this disorder, such as NAFLD. In recent years, global environmental climate change, the COVID-19 pandemic, the current war in Europe, and other conflicts have threatened food security and human nutrition worldwide. This further emphasizes the urgent need for sustainable sources of functional phytochemicals to be included in the food industry and dietary habits. This review summarizes the latest findings on selected phytochemicals from sustainable sources-algae and edible mushrooms-that affect the synthesis and metabolism of cholesterol and improve or prevent NAFLD.

Keywords:  NAFLD; NASH; active compounds; algae; cholesterol; fungi; inflammation; mushrooms; phytochemicals; sustainable

DOI:  https://doi.org/10.3390/ijms232213667
Molecules. 2022 Nov 21. pii: 8083. [Epub ahead of print]27(22):

An Overview of Antitumour Activity of Polysaccharides.

Hongzhen Jin, Maohua Li, Feng Tian, Fan Yu, Wei Zhao.

  Cancer incidence and mortality are rapidly increasing worldwide; therefore, effective therapies are required in the current scenario of increasing cancer cases. Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, and they have become the focus of current antitumour drug research owing to their significant antitumour effects. In addition to the direct antitumour activity of some natural polysaccharides, their structures offer versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent advances in natural polysaccharides and polysaccharide-based nanomedicines for cancer therapy.

Keywords:  anticancer; drug delivery systems; nanomedicines; polysaccharides

DOI:  https://doi.org/10.3390/molecules27228083
Biomed Pharmacother. 2022 Dec;pii: S0753-3322(22)01299-9. [Epub ahead of print]156 113910

Injectable rapidly dissolving needle-type gelatin implant capable of delivering high concentrations of H2O2 through intratumoral injection.

Sewon Park, Jungyu Kim, Changkyu Lee.

  Intratumoral injections can reduce systemic absorption and deliver large amounts of drugs to the tumor, thereby reducing side effects and exhibiting high therapeutic efficacy. Therefore, a variety of drug delivery systems, such as hydrogels, fine particles, and nanoparticles, have been studied. Although the sustained-release drug delivery system can effectively reduce systemic absorption due to the slow release of the drug from the site of intratumoral injection, it lacks the ability to deliver high concentrations of drugs to the tumor. In particular, the larger the tumor size, the lower the efficacy of the treatment. To address this problem, this study focused on the tumor structure. Owing to the three-dimensional structure of the dense tumor microenvironment (TME) and abnormal blood vessels, drugs administered directly into the tumor act as if they were encapsulated in a hydrogel. To evaluate whether the three-dimensional structure of the tumor affects the intratumoral distribution and systemic absorption of drugs, needle-type starch implants (GOD-NS implants) and needle-type gelatin implants (GOD-NG implants) containing glucose oxidase (GOD), a protein that exhibits anti-cancer effects through hydrogen peroxide (H2O2) generation, were prepared. Both GOD-NS and GOD-NG implants can be easily injected into tumors. GOD-NS implants released GOD slowly, whereas GOD-NG implants released most of the GOD within 1 h. When a GOD-NG implant that rapidly released GOD was also injected, a high concentration of GOD was maintained in the tumor for a long time as it was trapped in the three-dimensional structure of the tumor. This study demonstrated that intratumoral injection of a rapidly drug-releasing gelatin needle may be a novel drug delivery system capable of long-term retention of high drug concentrations in tumors, as the three-dimensional structure of the tumor affects drug delivery.

Keywords:  Gelatin; Glucose oxidase; Hydrogen peroxide generation; Implant; Intratumoral drug administration; Starch

DOI:  https://doi.org/10.1016/j.biopha.2022.113910
Molecules. 2022 Nov 08. pii: 7668. [Epub ahead of print]27(22):

Can Natural Products Targeting EMT Serve as the Future Anticancer Therapeutics?

Sirajudheen Anwar, Jonaid Ahmad Malik, Sakeel Ahmed, Verma Abhishek Kameshwar, Jowaher Alanazi, Abdulwahab Alamri, Nafees Ahemad.

  Cancer is the leading cause of death and has remained a big challenge for the scientific community. Because of the growing concerns, new therapeutic regimens are highly demanded to decrease the global burden. Despite advancements in chemotherapy, drug resistance is still a major hurdle to successful treatment. The primary challenge should be identifying and developing appropriate therapeutics for cancer patients to improve their survival. Multiple pathways are dysregulated in cancers, including disturbance in cellular metabolism, cell cycle, apoptosis, or epigenetic alterations. Over the last two decades, natural products have been a major research interest due to their therapeutic potential in various ailments. Natural compounds seem to be an alternative option for cancer management. Natural substances derived from plants and marine sources have been shown to have anti-cancer activity in preclinical settings. They might be proved as a sword to kill cancerous cells. The present review attempted to consolidate the available information on natural compounds derived from plants and marine sources and their anti-cancer potential underlying EMT mechanisms.

Keywords:  anticancer therapy; cancer; cancer EMT; chemotherapy; epithelial-mesenchymal transition; natural chemical entities

DOI:  https://doi.org/10.3390/molecules27227668
J Polym Environ. 2022 Nov 11. 1-20

Biodegradable PEG-PCL Nanoparticles for Co-delivery of MUC1 Inhibitor and Doxorubicin for the Confinement of Triple-Negative Breast Cancer.

Akanksha Behl, Subhash Solanki, Shravan K Paswan, Tirtha K Datta, Adesh K Saini, Reena V Saini, Virinder S Parmar, Vijay Kumar Thakur, Shashwat Malhotra, Anil K Chhillar.

  Combating triple-negative breast cancer (TNBC) is still a problem, despite the development of numerous drug delivery approaches. Mucin1 (MUC1), a glycoprotein linked to chemo-resistance and progressive malignancy, is unregulated in TNBC. GO-201, a MUC1 peptide inhibitor that impairs MUC1 activity, promotes necrotic cell death by binding to the MUC1-C unit. The current study deals with the synthesis and development of a novel nano-formulation (DM-PEG-PCL NPs) comprising of polyethylene glycol-polycaprolactone (PEG-PCL) polymer loaded with MUC1 inhibitor and an effective anticancer drug, doxorubicin (DOX). The DOX and MUC1 loaded nanoparticles were fully characterized, and their different physicochemical properties, viz. size, shape, surface charge, entrapment efficiencies, release behavior, etc., were determined. With IC50 values of 5.8 and 2.4 nm on breast cancer cell lines, accordingly, and a combination index (CI) of < 1.0, DM-PEG-PCL NPs displayed enhanced toxicity towards breast cancer cells (MCF-7 and MDA-MB-231) than DOX-PEG-PCL and MUC1i-PEG-PCL nanoparticles. Fluorescence microscopy analysis revealed DOX localization in the nucleus and MUC1 inhibitor in the mitochondria. Further, DM-PEG-PCL NPs treated breast cancer cells showed increased mitochondrial damage with enhancement in caspase-3 expression and reduction in Bcl-2 expression.In vivo evaluation using Ehrlich Ascites Carcinoma bearing mice explicitly stated that DM-PEG-PCL NPs therapy minimized tumor growth relative to control treatment. Further, acute toxicity studies did not reveal any adverse effects on organs and their functions, as no mortalities were observed. The current research reports for the first time the synergistic approach of combination entrapment of a clinical chemotherapeutic (DOX) and an anticancer peptide (MUC1 inhibitor) encased in a diblock PEG-PCL copolymer. Incorporating both DOX and MUC1 inhibitors in PEG-PCL NPs in the designed nanoformulation has provided chances and insights for treating triple-negative breast tumors. Our controlled delivery technology is biodegradable, non-toxic, and anti-multidrug-resistant. In addition, this tailored smart nanoformulation has been particularly effective in the therapy of triple-negative breast cancer.
Supplementary Information: The online version contains supplementary material available at 10.1007/s10924-022-02654-4.

Keywords:  Bcl-xL; Doxorubicin; Drug delivery system; MUC1 inhibitor; PEG-PCL; Triple-negative breast cancer

DOI:  https://doi.org/10.1007/s10924-022-02654-4
RSC Adv. 2022 Nov 09. 12(50): 32534-32551

Co-encapsulation of paclitaxel and 5-fluorouracil in folic acid-modified, lipid-encapsulated hollow mesoporous silica nanoparticles for synergistic breast cancer treatment.

Huanli Yin, Qi Yan, Yuan Liu, Lan Yang, Yang Liu, Yujie Luo, Tianyu Chen, Ningxi Li, Min Wu.

A dual-loaded multi-targeted drug delivery nanosystem was constructed to simultaneously load paclitaxel (PTX) and 5-fluorouracil (5-FU) for targeted delivery and sustained release at tumor sites. Hollow mesoporous silica nanoparticles (HMSNs) were prepared by the inverse microemulsion method, then modified with folic acid and pH- and temperature-responsive materials, co-loaded with PTX and 5-FU, and finally encapsulated into lipid membranes. The obtained nanosystem was selectively internalized by human breast cancer MCF-7 cells that overexpress folate receptors through an energy-dependent process, and it released both drugs in vitro in a simulated tumor microenvironment. Moreover, the inhibitory effect of the dual-loaded nanoparticles was significantly better than that of the free drugs, suggesting that the composite nanosystem has the potential to selectively target tumor sites and perform the synergistic effect of PTX and 5-FU, while reducing their toxic effects on normal tissues.

DOI: https://doi.org/10.1039/d2ra03718a
Int J Biol Macromol. 2022 Nov 17. pii: S0141-8130(22)02666-6. [Epub ahead of print]

Layer-by-layer development of chitosan/alginate-based platelet-mimicking nanocapsules for augmenting doxorubicin cytotoxicity against breast cancer.

Alaa Ibrahim, Islam A Khalil, Mohamed Y Mahmoud, Alaa F Bakr, Monira G Ghoniem, Eida S Al-Farraj, Ibrahim M El-Sherbiny.

  Breast carcinoma is considered one of the most invasive and life-threatening malignancies in females. Mastectomy, radiation therapy, hormone therapy and chemotherapy are the most common treatment choices for breast cancer. Doxorubicin (DOX) is one of the most regularly utilized medications in breast cancer protocols. However, DOX has showed numerous side effects including lethal cardiotoxicity. This study aims to fortify DOX cytotoxicity and lowering its side effects via its combining with the antidiabetic metformin (MET) as an adjuvant therapy, along with its effective delivery using natural platelet-rich plasma (PRP), and newly-developed PRP-mimicking nanocapsules (NCs). The PRP-mimicking NCs were fabricated via layer-by-layer (LBL) deposition of oppositely charged biodegradable and biocompatible chitosan (CS) and alginate (ALG) on a core of synthesized polystyrene nanoparticles (PS NPs) followed by removal of the PS core. Both natural PRP and PRP-mimicking NCs were loaded with DOX and MET adjuvant therapy, followed by their physicochemical characterizations including DLS, FTIR, DSC, and morphological evaluation using TEM. In-vitro drug release studies, cytotoxicity, apoptosis/necrosis, and cell cycle analysis were conducted using MCF-7 breast cancer cells. Also, an in-vivo assessment was carried out using EAC-bearing balb/c mice animal model to evaluate the effect of DOX/MET-loaded natural PRP and PRP-mimicked NCs on tumor weight, volume and growth biomarkers in addition to analyzing the immunohistopathology of the treated tissues. Results confirmed the development of CS/ALG-based PRP-mimicking NCs with a higher loading capacity of both drugs (DOX and MET) and smaller size (259.7 ± 19.3 nm) than natural PRP (489 ± 20.827 nm). Both in-vitro and in-vivo studies were in agreement and confirmed that MET synergized the anticancer activity of DOX against breast cancer. Besides, the developed LBL NCs successfully mimicked the PRP in improving the loaded drugs biological efficiency more than free drugs.

Keywords:  Alginate; Breast cancer; Chitosan; Doxorubicin; Layer-by-layer; Metformin; Nanocapsules; Platelet-rich plasma

DOI:  https://doi.org/10.1016/j.ijbiomac.2022.11.107
Drug Res (Stuttg). 2022 Nov 24.

Curcumin-Loaded Chitosan Nanoparticle Preparation and Its Protective Effect on Celecoxib-induced Toxicity in Rat isolated Cardiomyocytes and Mitochondria.

Hossein Ali Ebrahimi, Samira Esmaeli, Saleh Khezri, Ahmad Salimi.

Curcumin has a wide range of pharmacological activities, including antioxidant, anti-inflammatory and tissue protective. In here we hypothesized that curcumin-loaded chitosan-coated solid lipid nanoparticles (CuCsSLN) are able to increase its overall bioavailability and hence its antioxidant and mitochondria;/lysosomal protective properties of curcumin. CuCsSLN were prepared using solvent diffusion technique for formation of solid lipid nanoparticles (SLNs) and electrostatic coating of positive-charged chitosan to negative surface of SLNs. CuCsSLN showed the encapsulation efficiency of 91.4±2.7%, the mean particle size of 208±9 nm, the polydispersity index of 0.34±0.07, and the zeta potential of+53.5±3.7 mV. The scanning electron microscope (SEM) images of nanoparticles verified their nanometric size and also spherical shape. Curcumin was released from CuCsSLN in a sustain release pattern up to 24 hours. Then isolated cardiomyocytes and mitochondria were simultaneously treated with (1) control (0.05% ethanol), (2) celecoxib (20 µg/ml) treatment, (3) celecoxib (20 µg/ml)+++CuCsSLN (1 µg/ml) treatment, (4) CuCsSLN (1 µg/ml) treatment, (5) celecoxib (20 µg/ml)+++curcumin (10 µM) treatment and (6) curcumin (10 µM) treatment for 4 h at 37°C. The results showed that celecoxib (20 µg/ml) induced a significant increase in cytotoxicity, reactive oxygen species (ROS) formation, mitochondria membrane potential (ΔΨm) collapse, lipid peroxidation, oxidative stress and mitochondrial swelling while CuCsSLN and curcumin reverted the above toxic effect of celecoxib. Our data indicated that the effect of CuCsSLN in a number of experiments, is significantly better than that of curcumin which shows the role of chitosan nanoparticles in increasing effect of curcumin.

DOI: https://doi.org/10.1055/a-1960-3092
Biomed Pharmacother. 2022 Dec;pii: S0753-3322(22)01306-3. [Epub ahead of print]156 113917

Targeting hypoxia-related metabolism molecules: How to improve tumour immune and clinical treatment?

Bing Liang, Lin Deng, Xiuhua Zhou.

  Tumour metabolism has gradually come to be regarded as a key target to prevent tumour growth and metastasis. The unique metabolic characteristics of tumours enable them to maintain self-proliferation in abnormal environments. In recent years, the necessity of hypoxia in the tumour microenvironment has been gradually recognized, and hypoxia-induced tumour metabolites are also regarded as key therapeutic targets. How these hypoxia-related metabolites support tumour development, how to regulate the malignant process of tumours, and how to prevent tumour immune escape have become urgent problems that need to be solved. In this review, we summarize the characteristic tumour regulation of hypoxia-related metabolites and the mechanisms that promote immune escape of tumours. Finally, we summarize the relevant targeted inhibitors in an attempt to provide some novel therapeutic insights.

Keywords:  Clinical treatment; Hypoxia; Immune; Metabolism

DOI:  https://doi.org/10.1016/j.biopha.2022.113917
Cureus. 2022 Oct;14(10): e30411

Efficacy of Diclofenac Transdermal Patch in Therapeutic Extractions: A Literature Review.

Akshata Awachat, Deepankar Shukla, Nitin D Bhola.

  Diclofenac sodium is a nonsteroidal anti-inflammatory drug that effectively manages pain following therapeutic extractions. Post-extraction pain is commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs). In addition to their high bioavailability and long duration of action, transdermal NSAIDS have several other advantages. The review tries to understand and elucidate the use of transdermal patches, here Diclofenac, as a postoperative pain management modality. Drug delivery is one of the essential aspects of drug administration where transdermal patches are to be found equally effective when compared to oral administration of drugs. Various analgesics can be administered as patches, for example, ketoprofen, diclofenac, etc. There are also comparative studies between diclofenac and ketoprofen to see and understand the efficacy of transdermal patches compared with oral administration. Compared to oral administration, transdermal patches offer numerous benefits. These include avoidance of first-pass metabolism, sustained and non-rapid absorption, steady plasma levels that remain for prolonged periods, lack of patient dependence on drugs, prevention of gastric distress, and flexibility of stopping delivery of medications by simply removing the patch. This review aims to examine the diclofenac transdermal patch's effectiveness in reducing postoperative pain after orthodontic extraction.

Keywords:  diclofenac; efficacy; orthodontic extraction; rescue analgesia; transdermal patch

DOI:  https://doi.org/10.7759/cureus.30411
Metabolites. 2022 Nov 20. pii: 1145. [Epub ahead of print]12(11):

Recent Updates on Source, Biosynthesis, and Therapeutic Potential of Natural Flavonoid Luteolin: A Review.

Nandakumar Muruganathan, Anand Raj Dhanapal, Venkidasamy Baskar, Pandiyan Muthuramalingam, Dhivya Selvaraj, Husne Aara, Mohamed Zubair Shiek Abdullah, Iyyakkannu Sivanesan.

  Nature gives immense resources that are beneficial to humankind. The natural compounds present in plants provide primary nutritional values to our diet. Apart from food, plants also provide chemical compounds with therapeutic values. The importance of these plant secondary metabolites is increasing due to more studies revealing their beneficial properties in treating and managing various diseases and their symptoms. Among them, flavonoids are crucial secondary metabolite compounds present in most plants. Of the reported 8000 flavonoid compounds, luteolin is an essential dietary compound. This review discusses the source of the essential flavonoid luteolin in various plants and its biosynthesis. Furthermore, the potential health benefits of luteolins such as anti-cancer, anti-microbial, anti-inflammatory, antioxidant, and anti-diabetic effects and their mechanisms are discussed in detail. The activity of luteolin and its derivatives are diverse, as they help to prevent and control many diseases and their life-threatening effects. This review will enhance the knowledge and recent findings regarding luteolin and its therapeutic effects, which are certainly useful in potentially utilizing this natural metabolite.

Keywords:  anti-cancer; anti-diabetic; anti-inflammatory; flavonoid; luteolin; secondary metabolite

DOI:  https://doi.org/10.3390/metabo12111145
Front Chem. 2022 ;10 1069892

Editorial: Nanotechnology for natural products.

Jingshan S Du, Tongkai Chen, Fang Liu, Shengpeng Wang, Jinming Zhang, Ruoyu Zhang.



Keywords:  aptamers; conjugates; drug delivery; liposomes; nanoparticles; nanotechnology; natural products; peptides

DOI:  https://doi.org/10.3389/fchem.2022.1069892
Biomed Pharmacother. 2022 Dec;pii: S0753-3322(22)01340-3. [Epub ahead of print]156 113951

NF-κB inhibitors gifted by nature: The anticancer promise of polyphenol compounds.

Chengcheng Guan, Xintong Zhou, Huayao Li, Xiaoran Ma, Jing Zhuang.

  Polyphenol compounds are natural antioxidants, which are rich in anti-inflammatory and antioxidant components. They have a wide range of medicinal benefits that are believed to improve human health across various aspects; especially its anticancer effect has been gradually confirmed. The anticancer effect of polyphenols is mainly based on their strong antioxidant and immunomodulatory effects. The innate and adaptive immune responses as well as the development and maintenance of cells and tissues of the immune system are regulated by the NF-κB family of transcription factors. Dysregulation of NF-κB can lead to autoimmune diseases, chronic inflammation, and even cancer. Polyphenol compounds can exert antioxidant and immunomodulatory effects by targeting NF-κB, thus hindering the occurrence and development of tumors.Polyphenol compounds have unique advantages over conventional anticancer therapies such as chemotherapy because they have few side effects and do not cause toxicity to healthy cells. Additionally, they can attenuate the toxic effects of current anticancer therapies. Based on these characteristics, polyphenols have great potential in the prevention and treatment of cancer. This article systematically summarizes the mechanism of NF-κB in tumor genesis, progression, metastasis, angiogenesis, and drug resistance. In addition, we present the anticancer effect of polyphenol compounds by targeting NF-κB during the different stages of tumorigenesis.

Keywords:  Antioxidant; NF-κB; Polyphenol compounds; Transcription factor; Tumor

DOI:  https://doi.org/10.1016/j.biopha.2022.113951
J Am Nutr Assoc. 2022 Nov 23. 1-6

Nutritional Epigenetics and Phytochemicals in Cancer Formation.

Yasemin Açar, Gamze Akbulut.

  Nutrigenetics and nutrigenomics are two concepts in the area of nutritional genomics. Epigenetics is a new discipline with significant potential in the prevention and management of certain carcinomas and diseases. Epigenetics consists of DNA methylation, histone modification, non-coding RNAs, and telomerase activity. Epigenetic-based mechanisms act on the inhibition of cancer cells by modulating enzymes such as DNA methyltransferase and histone deacetylase, as well as non-coding RNAs. Phytochemicals are natural bioactive components of plant origin that have antioxidant, anti-inflammatory, and anti-angiogenic effects on various diseases, especially cancer. The epigenetic diet is a nutritional model based on the consumption of various phytochemicals such as epigallocatechin-3-gallate, morin, caffeic acid phenyl ester, apigenin, genistein, curcumin, resveratrol, and sulforaphane. Phytochemicals exert their effects on cancer-based by reducing cell proliferation, invasion, and metastasis and increasing cell apoptosis. Simultaneously, it has functions such as reducing oncogenes that have effects on cancer etiology and increasing tumor suppressor genes. Key teaching pointsCancer is a chronic disease with a high mortality rate, in which various genetic and environmental factors are involved in its etiology.Protooncogenes, tumor suppressor genes, and DNA repair genes are among the gene groups that form the basis of cancer and genetic structure.The bidirectional interaction between nutrition and the human genome has been effective in the emergence of the concepts of nutrigenetics and nutrigenomics.Epigenetic diet is a diet based on the consumption of foods such as soy, grapes, blueberries, turmeric, cruciferous vegetables, and green tea, which induce epigenetic mechanisms that protect against cancer and aging.

Keywords:  Cancer; nutrition; nutritional epigenetics; phytochemicals

DOI:  https://doi.org/10.1080/27697061.2022.2147106
Biomed Pharmacother. 2022 Dec;pii: S0753-3322(22)01334-8. [Epub ahead of print]156 113945

Anti-inflammatory and anti-allergic potential of dietary flavonoids: A review.

Allah Rakha, Nehal Umar, Roshina Rabail, Masood Sadiq Butt, Marek Kieliszek, Abdo Hassoun, Rana Muhammad Aadil.

  Chronic inflammation plays an imperative role in the onset and progression of chronic diseases including diabetes, hypertension, cancer, allergies, and asthma. Diet can modulate different stages of inflammation since it is a rich source of antioxidants and bioactive compounds. Flavonoids are bioactive compounds abundantly found in various food groups such as vegetables, fruits, nuts, cereals, and beverages. Recent work on flavonoids has unveiled their potential to regulate or inhibit inflammation. This is attributed to their anti-inflammatory, anti-oxidative, and immune-modulatory properties, making flavonoids an invaluable component in nutraceutical, pharmaceutical, and medicinal applications. However, information related to their anti-inflammatory mechanism is still not well understood. The current review is an attempt to elaborate chemical structure, dietary sources, and anti-inflammatory properties of flavonoids against allergic diseases.

Keywords:  Anti-allergic; Anti-inflammatory; Flavonoids; Kaempferol; Luteolin; Myricetin; Quercitin

DOI:  https://doi.org/10.1016/j.biopha.2022.113945
Int J Mol Sci. 2022 Nov 20. pii: 14427. [Epub ahead of print]23(22):

Recent Advances in Nanomaterials for Asthma Treatment.

Xu Zuo, Xiaoping Guo, Yinuo Gu, Haoyu Zheng, Zhengjie Zhou, Xinlei Wang, Shengyu Jiang, Guoqiang Wang, Caina Xu, Fang Wang.

  Asthma is a chronic airway inflammatory disease with complex mechanisms, and these patients often encounter difficulties in their treatment course due to the heterogeneity of the disease. Currently, clinical treatments for asthma are mainly based on glucocorticoid-based combination drug therapy; however, glucocorticoid resistance and multiple side effects, as well as the occurrence of poor drug delivery, require the development of more promising treatments. Nanotechnology is an emerging technology that has been extensively researched in the medical field. Several studies have shown that drug delivery systems could significantly improve the targeting, reduce toxicity and improve the bioavailability of drugs. The use of multiple nanoparticle delivery strategies could improve the therapeutic efficacy of drugs compared to traditional delivery methods. Herein, the authors presented the mechanisms of asthma development and current therapeutic methods. Furthermore, the design and synthesis of different types of nanomaterials and micromaterials for asthma therapy are reviewed, including polymetric nanomaterials, solid lipid nanomaterials, cell membranes-based nanomaterials, and metal nanomaterials. Finally, the challenges and future perspectives of these nanomaterials are discussed to provide guidance for further research directions and hopefully promote the clinical application of nanotherapeutics in asthma treatment.

Keywords:  asthma; biomedical polymers; drug delivery; nanomaterials; nanoparticles

DOI:  https://doi.org/10.3390/ijms232214427
Cancers (Basel). 2022 Nov 19. pii: 5691. [Epub ahead of print]14(22):

Amino Acids in Cancer and Cachexia: An Integrated View.

Maurizio Ragni, Claudia Fornelli, Enzo Nisoli, Fabio Penna.

  Rapid tumor growth requires elevated biosynthetic activity, supported by metabolic rewiring occurring both intrinsically in cancer cells and extrinsically in the cancer host. The Warburg effect is one such example, burning glucose to produce a continuous flux of biomass substrates in cancer cells at the cost of energy wasting metabolic cycles in the host to maintain stable glycemia. Amino acid (AA) metabolism is profoundly altered in cancer cells, which use AAs for energy production and for supporting cell proliferation. The peculiarities in cancer AA metabolism allow the identification of specific vulnerabilities as targets of anti-cancer treatments. In the current review, specific approaches targeting AAs in terms of either deprivation or supplementation are discussed. Although based on opposed strategies, both show, in vitro and in vivo, positive effects. Any AA-targeted intervention will inevitably impact the cancer host, who frequently already has cachexia. Cancer cachexia is a wasting syndrome, also due to malnutrition, that compromises the effectiveness of anti-cancer drugs and eventually causes the patient's death. AA deprivation may exacerbate malnutrition and cachexia, while AA supplementation may improve the nutritional status, counteract cachexia, and predispose the patient to a more effective anti-cancer treatment. Here is provided an attempt to describe the AA-based therapeutic approaches that integrate currently distant points of view on cancer-centered and host-centered research, providing a glimpse of several potential investigations that approach cachexia as a unique cancer disease.

Keywords:  amino acid; cachexia; cancer metabolism; nutrition; supplement

DOI:  https://doi.org/10.3390/cancers14225691
Nanomaterials (Basel). 2022 Nov 16. pii: 4029. [Epub ahead of print]12(22):

Preparation of 6-Mercaptopurine Loaded Liposomal Formulation for Enhanced Cytotoxic Response in Cancer Cells.

Alam Jamal, Amer H Asseri, Ehab M M Ali, Afnan H El-Gowily, Mohamed Imran Khan, Salman Hosawi, Reem Alsolami, Tarek A Ahmed.

  6-Mercaptopurine (6-MP) is a well-known immunosuppressive medication with proven anti-proliferative activities. 6-MP possesses incomplete and highly variable oral absorption due to its poor water solubility, which might reduce its anti-cancer properties. To overcome these negative effects, we developed neutral and positively charged drug-loaded liposomal formulations utilizing the thin-film hydration technique. The prepared liposomal formulations were characterized for their size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The average size of the prepared liposomes was between 574.67 ± 37.29 and 660.47 ± 44.32 nm. Positively charged liposomes (F1 and F3) exhibited a lower PDI than the corresponding neutrally charged ones (F2 and F4). Entrapment efficiency was higher in the neutral liposomes when compared to the charged formulation. F1 showed the lowest IC50 against HepG2, HCT116, and MCF-7 cancer cells. HepG2 cells treated with F1 showed the highest level of inhibition of cell proliferation with no evidence of apoptosis. Cell cycle analysis showed an increase in the G1/G0 and S phases, along with a decrease in the G2/M phases in the cell lines treated with drug loaded positively charged liposomes when compared to free positive liposomes, indicating arrest of cells in the S phase due to the stoppage of priming and DNA synthesis outside the mitotic phase. As a result, liposomes could be considered as an effective drug delivery system for treatment of a variety of cancers; they provide a chance that a nanoformulation of 6-MP will boost the cytotoxicity of the drug in a small pharmacological dose which provides a dosage advantage.

Keywords:  6-mercaptopurine; IC50; apoptosis; cell cycle phases; human cell lines; liposomes

DOI:  https://doi.org/10.3390/nano12224029
Molecules. 2022 Nov 11. pii: 7771. [Epub ahead of print]27(22):

Natural Reno-Protective Agents against Cyclosporine A-Induced Nephrotoxicity: An Overview.

Sabrin R M Ibrahim, Hossam M Abdallah, Ali M El-Halawany, Gamal A Mohamed, Aisha A Alhaddad, Waad A Samman, Ali A Alqarni, Akaber T Rizq, Kholoud F Ghazawi, Riham Salah El-Dine.

  CA (cyclosporine A) is a powerful immunosuppressing agent that is commonly utilized for treating various autoimmune illnesses and in transplantation surgery. However, its usage has been significantly restricted because of its unwanted effects, including nephrotoxicity. The pathophysiology of CA-induced kidney injury involves inflammation, apoptosis, tubular injury, oxidative stress, and vascular injury. Despite the fact that exact mechanism accountable for CA's effects is inadequately understood, ROS (reactive oxygen species) involvement has been widely proposed. At present, there are no efficient methods or drugs for treating CA-caused kidney damage. It is noteworthy that diverse natural products have been investigated both in vivo and in-vitro for their possible preventive potential in CA-produced nephrotoxicity. Various extracts and natural metabolites have been found to possess a remarkable potential for restoring CA-produced renal damage and oxidative stress alterations via their anti-apoptosis, anti-inflammatory, and antioxidative potentials. The present article reviews the reported studies that assess the protective capacity of natural products, as well as dietary regimens, in relation to CA-induced nephrotoxicity. Thus, the present study presents novel ideas for designing and developing more efficient prophylactic or remedial strategies versus CA passive influences.

Keywords:  cyclosporine A; natural products; nephrotoxicity; phenolics; reno-protective

DOI:  https://doi.org/10.3390/molecules27227771
Pharmaceutics. 2022 Nov 20. pii: 2527. [Epub ahead of print]14(11):

Quercetin Loaded Cationic Solid Lipid Nanoparticles in a Mucoadhesive In Situ Gel-A Novel Intravesical Therapy Tackling Bladder Cancer.

Sylvia Shawky, Shaimaa Makled, Ashraf Awaad, Nabila Boraie.

  The study aim was to develop an intravesical delivery system of quercetin for bladder cancer management in order to improve drug efficacy, attain a controlled release profile and extend the residence time inside the bladder. Either uncoated or chitosan coated quercetin-loaded solid lipid nanoparticles (SLNs) were prepared and evaluated in terms of colloidal, morphological and thermal characteristics. Drug encapsulation efficiency and its release behaviour were assessed. Furthermore, cytotoxicity of SLNs on T-24 cells was evaluated. Ex vivo studies were carried out using bovine bladder mucosa. Spherical SLNs (≈250 nm) ensured good entrapment efficiencies (EE > 97%) and sustained drug release up to 142 h. Cytotoxicity profile revealed concentration-dependent toxicity recording an IC50 in the range of 1.6-8.9 μg/mL quercetin. SLNs were further dispersed in in situ hydrogels comprising poloxamer 407 (20%) with mucoadhesive polymers. In situ gels exhibited acceptable gelation temperatures (around 25 °C) and long erosion time (24-27 h). SLNs loaded gels displayed remarkably enhanced retention on bladder tissues relative to SLNs dispersions. Coated SLNs exhibited better penetration abilities compared to uncoated ones, while coated SLNs dispersed in gel (G10C-St-QCT-SLNs-2) showed the highest penetration up to 350 μm. Hence, G10C-St-QCT-SLNs-2 could be considered as a platform for intravesical quercetin delivery.

Keywords:  T-24 cell lines; bladder cancer; coated SLNs; intravesical drug delivery; mucoadhesive in situ gel; quercetin

DOI:  https://doi.org/10.3390/pharmaceutics14112527
Front Genet. 2022 ;13 1039951

Ferroptosis in lymphoma: Emerging mechanisms and a novel therapeutic approach.

Qiao Zhou, Ting Li, Qin Qin, Xiaobo Huang, Yi Wang.

  Unlike apoptosis, necroptosis, autophagy, and pyroptosis, ferroptosis represents a new type of cell death, which is characterized by iron-dependent lipid peroxidation. This process relies largely on the metabolite reactive oxygen species (ROS), phospholipids containing polyunsaturated fatty acids (PUFA-PL), transition metal iron, intra-, and intercellular signaling events, and environmental stress that regulate cellular metabolism and ROS levels. Recent studies show that ferroptosis plays an important role in tumorigenesis, tumor development, and the treatment of hematological malignancies, including lymphoma. Despite the constant emergence of new drugs, the differences in morphological features, immunophenotypes, biological patterns, rates of onset, and response to treatment in lymphoma pose major therapeutic challenges. Since lymphoma is associated with ferroptosis and shows sensitivity towards it, targeting the potential regulatory factors may regulate lymphoma progression. This has emerged as a research hotspot. This review summarizes the current knowledge on ferroptosis induction and resistance mechanisms, their roles and mechanistic details of ferroptosis in lymphoma suppression and immunity, and finally the treatment strategies for lymphoma by targeting ferroptosis.

Keywords:  ferroptosis; ferroptosis inducer cell death; iron metabolism; lipid Metabolism; lymphoma; reactive oxygen species (ROS); therapeutic applications

DOI:  https://doi.org/10.3389/fgene.2022.1039951
Biomed Pharmacother. 2022 Dec;pii: S0753-3322(22)01321-X. [Epub ahead of print]156 113932

Engineered nanoparticles as emerging gene/drug delivery systems targeting the nuclear factor-κB protein and related signaling pathways in cancer.

Ramin Eskandani, Mohammad Kazempour, Raheleh Farahzadi, Zohreh Sanaat, Morteza Eskandani, Khosro Adibkia, Somayeh Vandghanooni, Ahad Mokhtarzadeh.

  The transcription factor nuclear factor-κB (NF-κB) is a critical regulator of the immune response, inflammation, cell growth, and survival. Canonical and non-canonical pathways, two NF-κB pathways, are activated through diverse stimulators and receptors. NF-κB activity is dysregulated in various inflammation-related diseases and cancers. It was found that the persistent NF-κB activity has a major role in proliferation, apoptosis inhibition, metastasis, and cell cycle disruption in cancer cells and also the survival of cancer stem cells (CSCs) within the tumors. Therefore, suppression of the NF-κB pathway could be a promising therapeutic target for cancer therapy. Different biological inhibitors (e.g., peptides, small molecules, antisense oligonucleotides (ASOs), and antibodies (Abs)) have been demonstrated to inhibit the NF-κB pathway. Low stability in the circulation system, weak availability, and poor cellular uptake of some inhibitors limit their therapeutic applications. To address these drawbacks nanocarrier systems are often formulated and applied in drug delivery as an effective therapeutic approach. Targeted nanosystems (i.e., small molecules, peptides, Abs and Aptamers (Aps) conjugated nanocarriers), as well as smart responsive nanocarriers, can improve the efficiency of therapeutics while reducing the off-target toxicity. This review describes the NF-κB signaling pathways and mechanisms of their over-activation in tumor initiation and progression. The NF-κB inhibitors and their clinical applications are also discussed. It also overviews different nanocarriers used as robust vehicles for the delivery of NF-κB inhibitors and anti-tumor agents to improve the bioavailability of drugs and selective targeting of cancer cells to repress NF-κB activity in tumor cells.

Keywords:  Cancer stem cells; Decoy NF-κB oligodeoxynucleotides; Humans; Inflammation; NF-kappa B; NF-κB inhibitors; Nanoparticles; Signal Transduction; Targeted therapy; Tumor necrosis factor receptor; Tumorgenesis

DOI:  https://doi.org/10.1016/j.biopha.2022.113932
Ther Deliv. 2022 Nov 23.

Formulation considerations for improving intranasal delivery of CNS acting therapeutics.

Darshana Patel, Hetal Thakkar.

  One of the principal impediments for the treatment of neurological conditions is the lack of ability of most of the medicinal agents to evade the blood-brain barrier. Among all the novel approaches to bypass the blood-brain barrier, nose to brain transport is the most patient compliant, non-invasive and effective approach. It directly transports drugs to the CNS via the trigeminal and olfactory nerves present in the nasal cavity. This review article focuses on anatomy and physiology of nasal cavity, potential of intranasal drug delivery, mechanisms of drug transport to brain, its advantages and limitations, novel intranasal formulations, marketed products, factors affecting nose to brain transport, formulation consideration of intranasal products and the future perspectives of CNS targeting via intranasal drug administration.

Keywords:  CNS disorders; blood–brain barrier; nose-to-brain transport of drugs; novel formulations

DOI:  https://doi.org/10.4155/tde-2022-0018
Int J Pharm. 2022 Nov 16. pii: S0378-5173(22)00962-0. [Epub ahead of print] 122407

Biologically inspired stealth - camouflaged strategies in nanotechnology for the improved therapies in various diseases.

Mohammad Imran, Vemana Gowd, Puspita Saha, Summya Rashid, Anis Ahmad Chaudhary, Marwa Yousry A Mohamed, Abdullah S Alawam, Rehan Khan.

  Nanotechnology has received increasing attention in the past decade and it's being used as a model for developing better treatments for a variety of diseases. Despite the fact that nanotechnology-based therapy has greatly improved treatment regimens, it still faces challenges such as inadequate circulation, insufficient accumulation at the target region, and undesired toxicity. In this regard, scientists are working on producing cell-membrane camouflaged nanoparticles as a biomimetic technique for modifying the surface of existing nanoparticles to produce significant therapeutic benefits following imparting myriad of desired functionalities. Membranes originating from erythrocytes, white blood cells, cancer cells, stem cells, platelets, or bacterial cells have been used to coat nanoparticle surfaces and create biologically inspired camouflaged nanoparticles. These biomemitic delivery systems have been proven to have potential applications in diagnosing and treating vaiorus diseases, including drug administration, immunisation, immunological regulation, and detoxification. From its inception to the present, we provide a complete description of this advanced technique for functionalizing nanoparticle surfaces. The method of making these membrane coated nanoparticles as well as their characterisation have been thoroughly discussed. Following that, we focused on the diversity of cell membranes derived from distinct cells in the evolution of nanoparticles, emphasising how these biologically inspired stealth - camouflaged techniques have led to increased therapeutic efficacy in a variety of disease states.

Keywords:  Biomedical applications; Cell membrane; Drug delivery; Nanodecoys; Nanoparticles

DOI:  https://doi.org/10.1016/j.ijpharm.2022.122407
Front Pharmacol. 2022 ;13 1043283

Ferroptosis: A new therapeutic target for bladder cancer.

Fan Zeng, Yunping Lan, Ning Wang, Xiaobo Huang, Qiao Zhou, Yi Wang.

  Bladder cancer (BC) is the most frequent type of urinary system cancer. The prognosis of BC is poor due to high metastasis rates and multidrug resistance. Hence, development of novel therapies targeting BC cell death is urgently needed. As a novel cell death type with strong antitumor potential, ferroptosis has been investigated by many groups for its potential in BC treatment. As an iron-dependent cell death process, ferroptosis is characterized by excessive oxidative phospholipids. The molecular mechanisms of ferroptosis include iron overload and the system Xc-GSH-GPX4 signaling pathway. A recent study revealed that ferroptosis is involved in the metastasis, treatment, and prognosis of BC. Herein, in this review, we comprehensively summarize the mechanism of ferroptosis, address newly identified targets involved in ferroptosis, and discuss the potential of new clinical therapies targeting ferroptosis in BC.

Keywords:  bladder cancer; ferroptosis; iron metabolism; metastasis; system Xc-GSH-GPX4 signaling pathway; treatment

DOI:  https://doi.org/10.3389/fphar.2022.1043283
Gels. 2022 Nov 15. pii: 741. [Epub ahead of print]8(11):

Developments on the Smart Hydrogel-Based Drug Delivery System for Oral Tumor Therapy.

Yiwen Zhao, Bei Ran, Xi Xie, Wanrong Gu, Xiuwen Ye, Jinfeng Liao.

  At present, an oral tumor is usually treated by surgery combined with preoperative or postoperative radiotherapies and chemotherapies. However, traditional chemotherapies frequently result in substantial toxic side effects, including bone marrow suppression, malfunction of the liver and kidneys, and neurotoxicity. As a new local drug delivery system, the smart drug delivery system based on hydrogel can control drug release in time and space, and effectively alleviate or avoid these problems. Environmentally responsive hydrogels for smart drug delivery could be triggered by temperature, photoelectricity, enzyme, and pH. An overview of the most recent research on smart hydrogels and their controlled-release drug delivery systems for the treatment of oral cancer is given in this review. It is anticipated that the local drug release method and environment-responsive benefits of smart hydrogels will offer a novel technique for the low-toxicity and highly effective treatment of oral malignancy.

Keywords:  drug delivery; localized chemotherapy; oral tumor; smart hydrogels; stimuli-responsive

DOI:  https://doi.org/10.3390/gels8110741
Gels. 2022 Nov 14. pii: 737. [Epub ahead of print]8(11):

Ginger Extract-Loaded Sesame Oil-Based Niosomal Emulgel: Quality by Design to Ameliorate Anti-Inflammatory Activity.

Marwa H Abdallah, Hanaa A Elghamry, Nasrin E Khalifa, Weam M A Khojali, El-Sayed Khafagy, Amr S Abu Lila, Hemat El-Sayed El-Horany, Shaimaa El-Housiny.

  Ginger, a natural plant belonging to the Zingeberaceae family, has been reported to have reasonable anti-inflammatory effects. The current study aimed to examine ginger extract transdermal delivery by generating niosomal vesicles as a promising nano-carrier incorporated into emulgel prepared with sesame oil. Particle size, viscosity, in vitro release, and ex vivo drug penetration experiments were performed on the produced formulations (ginger extract loaded gel, ginger extract loaded emulgel, ginger extract niosomal gel, and ginger extract niosomal emulgel). Carrageenan-induced edema in rat hind paw was employed to estimate the in vivo anti-inflammatory activity. The generated ginger extract formulations showed good viscosity and particle size. The in vitro release of ginger extract from niosomal formulation surpassed other formulations. In addition, the niosomal emulgel formulation showed improved transdermal flux and increased drug permeability through rabbit skin compared to other preparations. Most importantly, carrageenan-induced rat hind paw edema test confirmed the potential anti-inflammatory efficacy of ginger extract niosomal emulgel, compared to other formulations, as manifested by a significant decrease in paw edema with a superior edema inhibition potency. Overall, our findings suggest that incorporating a niosomal formulation within sesame oil-based emulgel might represent a plausible strategy for effective transdermal delivery of anti-inflammatory drugs like ginger extract.

Keywords:  anti-inflammatory effect; emulgel; ginger extract; niosomes; quality by design; sesame oil

DOI:  https://doi.org/10.3390/gels8110737
Asian J Pharm Sci. 2022 Nov 17.

Liposomes and liposome-like nanoparticles: From anti-fungal infection to the COVID-19 pandemic treatment.

Yonglong He, Wanting Zhang, Qingqing Xiao, Lifang Fan, Dechun Huang, Wei Chen, Wei He.

  The liposome is the first nanomedicine transformed into the market and applied to human patients. Since then, such phospholipid bilayer vesicles have undergone technological advancements in delivering small molecular-weight compounds and biological drugs. Numerous investigations about liposome uses were conducted in different treatment fields, including anti-tumor, anti-fungal, anti-bacterial, and clinical analgesia, owing to liposome's ability to reduce drug cytotoxicity and improve the therapeutic efficacy and combinatorial delivery. In particular, two liposomal vaccines were approved in 2021 to combat COVID-19. Herein, the clinically used liposomes are reviewed by introducing various liposomal preparations in detail that are currently proceeding in the clinic or on the market. Finally, we will discuss the challenges of developing liposomes and cutting-edge liposomal delivery for biological drugs and combination therapy.

Keywords:  COVID-19 pandemic; Clinical application; Drug delivery; Liposomes

DOI:  https://doi.org/10.1016/j.ajps.2022.11.002
Crit Rev Food Sci Nutr. 2022 Nov 22. 1-26

Caffeine-loaded nano/micro-carriers: Techniques, bioavailability, and applications.

Rezvan Shaddel, Safoura Akbari-Alavijeh, Ilaria Cacciotti, Shima Yousefi, Merve Tomas, Esra Capanoglu, Ozgur Tarhan, Ali Rashidinejad, Atefe Rezaei, Mohammed Bhia, Seid Mahdi Jafari.

  Caffeine, as one of the most consumed bioactive compounds globally, has gained considerable attention during the last years. Considering the bitter taste and adverse effects of high levels of caffeine consumption, it is crucial to apply a strategy for masking the caffeine's bitter taste and facilitating its programmable deliverance within a long time. Other operational parameters such as food processing parameters, exposure to sunlight and oxygen, and gastrointestinal digestion could also degrade the phenolic compounds in general and caffeine in special. To overcome these challenges, various nano/micro-platforms have been fabricated, including lipid-based (e.g., nanoliposomal vehicles; nanoemulsions, double emulsions, Pickering emulsions; microemulsions; niosomal vehicles; solid lipid nanoparticles and nanostructured lipid carriers), as well as biopolymeric (e.g., nanoparticles; hydrogels, organogels, oleogels; nanofibers and nanotubes; protein-polysaccharide nanocomplexes, conjugates; cyclodextrin inclusion complexes) and inorganic (e.g., gold and silica nanoparticles) nano/micro-structures. In this review, the findings on various caffeine-loaded nano/micro-carriers and their potential applications in functional food products/supplements will be discussed. Also, the controlled release and bioavailability of encapsulated caffeine will be given, and finally, the toxicity and safety of encapsulated caffeine will be presented.

Keywords:  Bioavailability; caffeine; encapsulation; functional foods; nano/micro-delivery systems

DOI:  https://doi.org/10.1080/10408398.2022.2147143
Crit Rev Food Sci Nutr. 2022 Nov 23. 1-18

Enzymatic lipophilization of bioactive compounds with high antioxidant activity: a review.

Mohsen Mardani, Katalin Badakné, Jamshid Farmani, Fereidoon Shahidi.

  Food products contain bioactive compounds such as phenolic and polyphenolic compounds and vitamins, resulting in a myriad of biological characteristics such as antimicrobial, anticarcinogenic, and antioxidant activities. However, their application is often restricted because of their relatively low solubility and stability in emulsions and oil-based products. Therefore, chemical, enzymatic, or chemoenzymatic lipophilization of these compounds can be achieved by grafting a non-polar moiety onto their polar structures. Among different methods, enzymatic modification is considered environmentally friendly and may require only minor downstream processing and purification steps. In recent years, different systems have been suggested to design the synthetic reaction of these novel products. This review presents the new trends in this area by summarizing the essential enzymatic modifications in the last decade that led to the synthesis of bioactive compounds with attractive antioxidative properties for the food industry by emphasizing on optimization of the reaction conditions to maximize the production yields. Lastly, recent developments regarding characterization, potential applications, emerging research areas, and needs are highlighted.

Keywords:  Antioxidants; bioactive compounds; enzymatic; lipophilization; optimization

DOI:  https://doi.org/10.1080/10408398.2022.2147268
IET Nanobiotechnol. 2022 Nov 24.

The anti-cancer effect of chitosan/resveratrol polymeric nanocomplex against triple-negative breast cancer; an in vitro assessment.

Azam Bozorgi, Zahra Haghighi, Mohammad Rasool Khazaei, Maryam Bozorgi, Mozafar Khazaei.

  Herein, the authors synthesised chitosan nanoparticles (Cs NPs) as a resveratrol (RSV) carrier and evaluated their efficacy in stimulating apoptosis in MDA-MB 231 cells. Blank (Cs NPs) and RSV- Cs NPs (RSV-Cs NPs) were synthesised via ionic gelation and characterised by using fourier-transform infrared spectroscopy (FTIR), Scanning electron microscope, dynamic light scattering/Zeta potential and RSV release. MDA-MB 231 cells were treated with RSV, Cs NPs and RSV-Cs NPs (24, 48, and 72 h), followed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Cell toxicity was evaluated using lactate dehydrogenase assay, and real-time polymerase chain reaction was performed to explore apoptosis induction. FTIR spectra confirmed the NPs via the formation of cross-linking bonds. Cs and RSV-Cs NPs sizes were about 75 and 198 nm with 14 and 24 mV zeta potentials. The RSV entrapment efficiency was 52.34 ± 0.16%, with an early rapid release followed by a sustained manner. Cs and RSV-Cs NPs inhibited cell proliferation at lower concentrations and IC50 values. RSV-Cs NPs had the most cytotoxic effect and stimulated intrinsic apoptotic pathway, indicated by increased Bcl-2-associated x (BAX), BAX/Bcl-2 ratio, P53 expressions, reduced Bcl-2 and upregulated caspases 3, 8 and 9. RSV-Cs NPs have a great potential to suppress invasive breast cancer cell proliferation by targeting mitochondrial metabolism and inducing the intrinsic apoptotic pathway.

Keywords:  apoptosis; breast cancer; chitosan nanoparticles; resveratrol

DOI:  https://doi.org/10.1049/nbt2.12108
Pharmaceuticals (Basel). 2022 Nov 19. pii: 1431. [Epub ahead of print]15(11):

Naringin's Prooxidant Effect on Tumor Cells: Copper's Role and Therapeutic Implications.

Mohd Farhan.

  Plant-derived polyphenolic chemicals are important components of human nutrition and have been found to have chemotherapeutic effects against a variety of cancers. Several studies in animal models have proven polyphenols' potential to promote apoptosis and tumor regression. However, the method by which polyphenols show their anticancer effects on malignant cells is not well understood. It is generally known that cellular copper rises within malignant cells and in the serum of cancer patients. In this communication, investigations reveal that naringin (a polyphenol found in citrus fruits) can strongly suppress cell proliferation and trigger apoptosis in various cancer cell lines in the presence of copper ions. The cuprous chelator neocuproine, which confirms copper-mediated DNA damage, prevents such cell death to a large extent. The studies further show that the cellular copper transporters CTR1 and ATP7A have a role in the survival dynamics of malignant cells after naringin exposure. The findings emphasize the crucial function of copper dynamics and mobilization in cancer cells and pave the path for a better understanding of polyphenols as nutraceutical supplements for cancer prevention and treatment.

Keywords:  DNA damage; cell death; copper; naringin; tumor microenvironment

DOI:  https://doi.org/10.3390/ph15111431
Front Oncol. 2022 ;12 1049494

Editorial: Sphingolipid metabolism and cancer.

Margarita M Ivanova, Irina U Agoulnik, Matilde E LLeonart.



Keywords:  anticancer therapy; cancer; ceramide; metabolism; sphingolipid

DOI:  https://doi.org/10.3389/fonc.2022.1049494
Biomed Pharmacother. 2022 Nov 16. pii: S0753-3322(22)01374-9. [Epub ahead of print]157 113985

The application of antidepressant drugs in cancer treatment.

Yunxi Zheng, Xu Chang, Yuyang Huang, Dingwen He.

  Antidepressants refer to psychotropic drugs which are used to treat mental illness with prominent emotional depression symptoms. It was reported that antidepressants had associated with anti-carcinogenic function which was associated with various signaling pathways and changing of microenvironment. Its mechanism includes cell apoptosis, antiproliferative effects, mitochondria-mediated oxidative stress, DNA damaging, changing of immune response and inflammatory conditions, and acting by inhibiting multidrug resistance of cancer cells. Accumulated studies showed that antidepressants influenced the metabolic pathway of tumor cells. This review summarized recent developments with the impacts and mechanisms of 10 kinds of antidepressants in carcinostasis. Antidepressants are also used in combination therapy with typical anti-tumor drugs which shows a synergic effect in anti-tumor. By contrast, the promotion roles of antidepressants in increasing cancer recurrence risk, mortality, and morbidity are also included. Further clinical experiments and mechanism analyses needed to be achieved. A full understanding of the underlying mechanisms of antidepressants-mediated anticarcinogenic effects may provide new clues for cancer prevention and clinical treatment.

Keywords:  Antidepressants; Cancer cells metabolism; Cancer treatment; Carcinostasis; Molecular mechanisms

DOI:  https://doi.org/10.1016/j.biopha.2022.113985