bims-kracam Biomed News
on K-Ras in cancer metabolism
Issue of 2022–03–20
83 papers selected by
Yasmin Elkabani, Egyptian Foundation for Research and Community Development



  1. ACS Appl Bio Mater. 2022 Mar 17.
      Iron oxide nanoparticles can induce cell death due to the ferroptosis mechanism, showing a great potential for cancer therapy. Here, we synthesized different-sized iron oxide nanoparticles (2-100 nm) to investigate their antitumor effect and toxicity mechanism. It was found that ultrasmall nanoparticles (< ∼5 nm) could accumulate in nucleus and were more efficient in triggering the generation of •OH than larger nanoparticles due to the quicker release of Fe2+, thus exhibiting more remarkable cytotoxicity. Nevertheless, 10 nm iron oxide nanoparticles group displayed the best antitumor effect in vivo. We studied the in vivo and intratumoral biodistribution of the nanoparticles and found that the therapeutic effects were related to both the tumoral accumulation and intratumoral distribution of nanoparticles. This work indicates the appropriate size of Fe3O4 NPs for cancer treatment and illustrates the possible factors that influence the therapeutic effect, suggesting the great potential of iron oxide in clinical application.
    Keywords:  biodistribution; cancer therapy; ferroptosis; iron oxide nanoparticles; reactive oxygen species
    DOI:  https://doi.org/10.1021/acsabm.2c00068
  2. Front Pharmacol. 2022 ;13 797804
      Cancer is the main cause of morbidity and mortality worldwide, excluding infectious disease. Because of their lack of specificity in chemotherapy agents are used for cancer treatment, these agents have severe systemic side effects, and gradually lose their therapeutic effects because most cancers become multidrug resistant. Platinum nanoparticles (PtNPs) are relatively new agents that are being tested in cancer therapy. This review covers the various methods for the preparation and physicochemical characterization of PtNPs. PtNPs have been shown to possess some intrinsic anticancer activity, probably due to their antioxidant action, which slows tumor growth. Targeting ligands can be attached to functionalized metal PtNPs to improve their tumor targeting ability. PtNPs-based therapeutic systems can enable the controlled release of drugs, to improve the efficiency and reduce the side effects of cancer therapy. Pt-based materials play a key role in clinical research. Thus, the diagnostic and medical industries are exploring the possibility of using PtNPs as a next-generation anticancer therapeutic agent. Although, biologically prepared nanomaterials exhibit high efficacy with low concentrations, several factors still need to be considered for clinical use of PtNPs such as the source of raw materials, stability, solubility, the method of production, biodistribution, accumulation, controlled release, cell-specific targeting, and toxicological issues to human beings. The development of PtNPs as an anticancer agent is one of the most valuable approaches for cancer treatment. The future of PtNPs in biomedical applications holds great promise, especially in the area of disease diagnosis, early detection, cellular and deep tissue imaging, drug/gene delivery, as well as multifunctional therapeutics.
    Keywords:  cancer; cancer therapy; delivery systems; nanoparticle; platinum nanoparticles
    DOI:  https://doi.org/10.3389/fphar.2022.797804
  3. Int J Biol Sci. 2022 ;18(4): 1695-1705
      Ferroptosis, a new form of programmed necrosis characterized by iron-dependent lethal accumulation of lipid hydroperoxides, is associated with many human diseases. Targeting amino acid (AA) availability can selectively suppress tumor growth and has been a promising therapeutic strategy for cancer therapy. Compelling studies have indicated that AA metabolism is also involved in ferroptosis, closely regulating its initiation and execution. This manuscript systematically summarizes the latest advances of AA metabolism in regulating ferroptosis and discusses the potential combination of therapeutic strategies that simultaneously target AA metabolism and ferroptosis in cancer to eliminate tumors or limit their invasiveness.
    Keywords:  amino acid metabolism; cancer; combinatorial therapy; ferroptosis
    DOI:  https://doi.org/10.7150/ijbs.64982
  4. Crit Rev Biotechnol. 2022 Mar 13. 1-22
      Mangrove plants, also known as halophytes, are ecologically important plants that grow in various tropical and subtropical intertidal regions. Owing to the extreme abiotic and biotic stressful conditions they thrive in, these plants produce unique compounds with promising pharmacological propensities. Mangroves are inhabited by an astronomical number of fungal communities which produce a diverse array of extracellular degradative enzymes, namely: amylase, cellulase, xylanase, pectinase, cholesterol oxidase, etc. Such enzymes can be isolated from the mangrove fungi and harnessed for different biotechnological applications, for example, as replacements for chemical catalysts. Mangrove microbes attract considerable attention as they shelter the largest group of marine microorganisms that are resistant to extreme conditions and can produce novel biogenic substances. Vaccines developed from mangrove microbes may promise a safe future by developing effective immunization procedures with a minimum of economic burden. Interestingly, mangroves offer an exciting opportunity for synthesizing nanoparticles in a greener way as these plants are naturally rich in phytochemicals. Rhizophora mucronata Lam., Avicennia officinalis L. and Excoecaria agallocha L. are capable of synthesizing nanoparticles which have evolved recently as an alternative in various industries and are used for their biomedical application. Besides, the phytoconstituents isolated from mangrove plants, such as: gallic acid, galactose, lupeol, catechins, carotenoids, etc., were explored for various biological activities. These compounds are used in the pharmaceutical and nutraceutical industries to produce antimicrobial, antioxidant, anticancer, antidiabetic, and other therapeutic agents. The present review provides information on the biotechnological potentials of mangrove plants and their bioactive compounds as a new source of novel drugs, enzymes, nanoparticles and therapeutically important microbial pigments. Thus, this review forms a base of support and hasten the urgent research on biomedical applications of mangroves.
    Keywords:  Biomedical applications; enzymes; halophytes; medicinal plants; microbes; nanoparticles; natural products; pharmaceuticals; vaccines
    DOI:  https://doi.org/10.1080/07388551.2022.2033682
  5. Eur J Pharmacol. 2022 Mar 09. pii: S0014-2999(22)00121-2. [Epub ahead of print] 174860
       OBJECTIVE: To explore inhibitory effect of iron oxide nanoparticles loaded with paclitaxel (IONP@PTX) on glioblastoma (GBM) and its potential mechanism.
    METHODS: IONP@PTX was synthesized and the characteristics were assessed by chemico-physical analysis and observed directly under transmission electron microscope. U251 cells and HMC3 cells were separately incubated with IONP@PTX and PTX, and then cell viability was detected by Cell Counting Kit-8. The capacity of cell invasive and migration was verified by Scratch wound healing and Transwell migration and invasion assays. Expressions levels of autophagy and ferroptosis biomarkers were demonstrated by Western blotting assay. Intracellular reactive oxygen species (ROS) and lipid peroxidation were detected with DCFH-DA and C11-BODIPY staining, respectively. Intracellular concentration of iron ions was quantified spectrophotometrically. Moreover, inhibitory effect of IONP@PTX on GBM was evaluated by monitoring tumor growth and the toxicity of IONP@PTX was evaluated by measuring the body weight and index of liver and spleen in the mice bearing GBM xenograft.
    RESULTS: The successfully synthesized IONP@PTX possesses a hydrate diameter about 36 nm and a core diameter around 10 nm. IONP@PTX exerted an inhibitory effect on U251 cells, but had little effect on HMC3 cells compared with PTX alone. In addition, IONP@PTX inhibited the capacity of cell migration and invasion, increased the levels of iron ions, ROS and lipid peroxidation, enhanced the expression of autophagy-related protein Beclin1 and LC3II, and suppressed the expression of p62 and ferroptosis-related protein GPX4 in vitro compared with control group. Moreover, administration of IONP@PTX suppressed tumor volume of GBM xenografts and decreased the expression level of GPX4 protein in tumor tissues in comparison with control group (All P < 0.05). Intriguingly, the effect of IONP@PTX on GBM could be weakened by additional 3-MA or enhanced by additional rapamycin in vitro and in vivo (P < 0.05). More importantly, IONP@PTX had no obvious toxic effect on mice bearing GBM xenograft.
    CONCLUSION: IONP@PTX inhibits GBM growth by enhancing autophagy-dependent ferroptosis pathway, thus it might become a potential ferroptosis-inducing agent for ferroptosis-based tumor therapy.
    Keywords:  Autophagy; Ferroptosis; Glioblastoma; Iron oxide nanoparticles; Paclitaxel
    DOI:  https://doi.org/10.1016/j.ejphar.2022.174860
  6. Small. 2022 Mar 15. e2200897
      Synergistic therapy for malignant tumors has been developed in the past. However, several disadvantages that are associated with the applied inorganic nanoagents cannot be avoided, including intrinsic systemic toxicity, immunosuppression, and low therapeutic efficiency. Herein, a biocompatible, multifunctional, inorganic nanoagent that simultaneously integrates chemodynamic, starvation, and photothermal therapies is developed. This nanoagent effectively converts endogenous H2 O2 into highly toxic hydroxyl radicals via the Fenton reaction. Self-reinforced cancer therapy is achieved via the scavenging of intracellular glutathione and glucose. The encapsulation of nanoagent by erythrocytes drastically reduces its immune recognition by macrophages. Thus, an augmented anti-tumor immune response is realized. Moreover, in contrast to traditional inorganic chemodynamic nanomaterials, the nanoagent has outstanding photothermal efficiency. Therefore, the present system exhibits an effective tumor therapeutic outcome. This work may facilitate a new pathway for the development of highly efficacious synergetic therapies.
    Keywords:  antitumor immunity; cancer therapy; chemodynamic performance; inorganic nanoagents; photo-thermal effects
    DOI:  https://doi.org/10.1002/smll.202200897
  7. Photodiagnosis Photodyn Ther. 2022 Mar 11. pii: S1572-1000(22)00090-4. [Epub ahead of print] 102801
       BACKGROUND/AIMS: Silica nanoparticles (SiNPs) have been promising vehicles for drug delivery. Cichorium Pumilum (CP), a natural photosensitizer (PS), has been reported to have many useful effects in cancer treatment. However, the poor water solubility and its low bioavailability have confined its use as a suitable photosensitizer for photodynamic therapy. Therefore, a subtle approach is required to overcome these drawbacks.
    MATERIALS AND METHODS: We have synthesized a silica nanoparticles loaded with Cichorium Pumilum. The nanoparticles structural morphologies have been charectrized by Transmission Electron Microscopy (TEM). The cytotoxicity for different concentrations of naked and encapsulated CP was evaluated. Moreover, the optimal concentration of naked and encapsulated CP with exposure time to a light (Maximum intensity at 350nm ∼0.27mW/cm2) required to eliminate the used cells (Osteosarcoma cells) were also measured.
    RESULTS: The results showed that encapsulated CP in SiNPs exhibited relatively higher efficacy than the naked CP by + 157.14 % of exposure time efficacy and + 49.45% of concentration efficacy, and encapsulated CP was also confirmed to be effective in eradicating osteosarcoma cells.
    CONCLUSION: The engineered silica nanoparticles loaded with CP enhanced the photodynamic therapy by increasing the CP bioavailability.
    Keywords:  Cichorium Pumilum; Encapsulation; Osteosarcoma Cells; Photodynamic Therapy; Silica Nanoparticles
    DOI:  https://doi.org/10.1016/j.pdpdt.2022.102801
  8. J Gastrointest Cancer. 2022 Mar 14.
       PURPOSE: Among all forms of cancers, hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. There are several treatment options for HCC ranging from loco-regional therapy to surgical treatment. Yet, there is high morbidity and mortality. Recent research focus has shifted towards more effective and less toxic cancer treatment options. Curcumin, the active ingredient in the Curcuma longa plant, has gained widespread attention in recent years because of its multifunctional properties as an antioxidant, anti-inflammatory, antimicrobial, and anticancer agent.
    METHODS: A systematic search of PubMed, Embase and Google Scholar was performed for studies reporting incidence of HCC, risk factors associated with cirrhosis and experimental use of curcumin as an anti-cancer agent.
    RESULTS: This review exclusively encompasses the anti-cancer properties of curcumin in HCC globally and it's postulated molecular targets of curcumin when used against liver cancers.
    CONCLUSIONS: This review is concluded by presenting the current challenges and future perspectives of novel plant extracts derived from C. longa and the treatment options against cancers.
    Keywords:  Anticancer; Cancer; Curcumin; Hepatocellular Carcinoma
    DOI:  https://doi.org/10.1007/s12029-022-00809-z
  9. Int J Pharm. 2022 Mar 10. pii: S0378-5173(22)00210-1. [Epub ahead of print]618 121655
      Doxycycline (DX) is a well-established antimicrobial drug that has been used since 1967 to treat several diseases. This drug has a wide therapeutic range, acting as antibacterial, antiviral, antiparasitic, and anticancer agent, including its neuroprotective, anti-inflammatory, and wound healing effects. However, DX is unstable in the physiological environment, presenting poor cellular penetration and adverse effects related to gastrointestinal irritation. As for practically all antibiotics, bacteria can develop resistance to this drug. Pharmaceutical nanotechnology proved to be a promising strategy to overcome these drawbacks. Thus, this review addresses scientific studies regarding formulations of DX-loaded nanoparticles (DX-NPs) for therapy use. Formulations with different materials, manufacturing methods, and biomedical applications are described and discussed to understand NPs contribution for in vitro and in vivo DX performance.
    Keywords:  Doxycycline; Drug delivery systems; Inorganic; Lipid; Metallic; Nanoparticle; Polymeric
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.121655
  10. Biomol Concepts. 2022 Mar 19. 13(1): 126-147
      Photodynamic therapy (PDT) is a clinically approved procedure that can exert a curative action against malignant cells. The treatment implies the administration of a photoactive molecular species that, upon absorption of visible or near infrared light, sensitizes the formation of reactive oxygen species. These species are cytotoxic and lead to tumor cell death, damage vasculature, and induce inflammation. Clinical investigations demonstrated that PDT is curative and does not compromise other treatment options. One of the major limitations of the original method was the low selectivity of the photoactive compounds for malignant over healthy tissues. The development of conjugates with antibodies has endowed photosensitizing molecules with targeting capability, so that the compounds are delivered with unprecedented precision to the site of action. Given their fluorescence emission capability, these supramolecular species are intrinsically theranostic agents.
    Keywords:  Targeted photodynamic therapy; antibody; cancer; fluorescence; photosensitizer; reactive oxygen species
    DOI:  https://doi.org/10.1515/bmc-2022-0010
  11. Biomed Res Int. 2022 ;2022 5425485
      Cancer is one of the primary causes of mortality globally, and the discovery of new anticancer drugs is the most important need in recent times. Natural products have been recognized as effective in fight against various diseases including cancer for over 50 years. Plants and microbes are the primary and potential sources of natural compounds to fight against cancer. Moreover, researches in the field of plant-based natural compounds have moved towards advanced and molecular level understandings from the last few decades, leading to the development of potent anticancer agents. Also, plants have been accepted as abundant and prosperous sources for the development of novel therapeutic agents for the management and prevention of different cancer types. The high toxicity of some cancer chemotherapy drugs, as well as their unfavorable side effects and drugs resistance, drives up the demand for natural compounds as new anticancer drugs. In this detailed evidence-based mechanistic review, facts and information about various medicinal plants, their bioactive compounds with their potent anticancer activities against different cancers have been gathered, with further approach to represent the molecular mechanism behind the anticancer activity of these plants. This review will be beneficial for investigators/scientists globally involved in the development of natural, safe, effective, and economical therapeutic agents/drugs against various cancers. This might be an important contribution in the field of drug discovery, where drugs can be used alone or in combination to increase the efficacy of newly synthesized drugs.
    DOI:  https://doi.org/10.1155/2022/5425485
  12. J Integr Med. 2022 Mar 01. pii: S2095-4964(22)00030-9. [Epub ahead of print]
      Metabolic syndrome (MS) involves people with the following risk factors: obesity, hypertension, high glucose level and hyperlipidemia. It can increase the risk of heart disease, stroke and type 2 diabetes mellitus. The prevalence of MS in the world's adult population is about 20%-25%. Today, there is much care to use medicinal plants. Turmeric (Curcuma longa) as well as curcumin which is derived from the rhizome of the plant, has been shown beneficial effects on different components of MS. Thus, the purpose of this manuscript was to introduce different in vitro, in vivo and human studies regarding the effect of turmeric and its constituent on MS. Moreover, different mechanisms of action by which this plant overcomes MS have been introduced. Based on studies, turmeric and its bioactive component, curcumin, due to their anti-inflammatory and antioxidant properties, have antidiabetic effects through increasing insulin release, antihyperlipidemic effects by increasing fatty acid uptake, anti-obesity effects by decreasing lipogenesis, and antihypertensive effects by increasing nitric oxide. According to several in vivo, in vitro and human studies, it can be concluded that turmeric or curcumin has important values as a complementary therapy in MS. However, more clinical trials should be done to confirm these effects.
    Keywords:  Curcuma longa; Curcumin; Diabetes; Hyperlipidemia; Metabolic syndrome; Turmeric
    DOI:  https://doi.org/10.1016/j.joim.2022.02.008
  13. Nanomedicine. 2022 Mar 14. pii: S1549-9634(22)00035-1. [Epub ahead of print] 102549
      Hypoxia enhances tumor aggressiveness thereby reducing the efficacy of anticancer therapies. Phytomedicine which is nowadays considered as the new panacea owing to its dynamic physiological properties is often plagued by shortcomings. Incorporating these wonder drugs in nanoparticles (phytonanomedicine) for hypoxia therapy is a new prospect in the direction of cancer management. Similarly, the concept of phytonanotheranostics for the precise tumor lesion detection and treatment monitoring in the hypoxic scenario is going on a rampant speed. In the same line, smart nanoparticles which step in for "on-demand" drug release based on internal or external stimuli are also being explored as a new tool for cancer management. However, studies regarding these smart and tailor-made nanotheranostics in the hypoxic tumor microenvironment are very limited. The present review is an attempt to collate about these smart stimuli-responsive phytonanotherapeutics in one place for initiating future research in this upcoming field for better cancer treatment.
    Keywords:  Hypoxia; Nanotheranostics; Phytochemicals; Phytonanomedicine; Responsive nanotheranostics
    DOI:  https://doi.org/10.1016/j.nano.2022.102549
  14. Int J Biol Macromol. 2022 Mar 12. pii: S0141-8130(22)00508-6. [Epub ahead of print]
      Folic acid is a synthetic form of folate widely used for food fortification. However, its bioavailability is limited due to its inherent instability at several conditions. Therefore, a suitable encapsulation system is highly required. In the present study, the fabrication condition for folic acid-loaded chitosan nanoparticle (FA-Chi-NP) was optimized and then subjected to characterization. The optimized formulation had the particle size, zeta potential, and encapsulation efficiency of 180 nm, +52 mV, and 90%, respectively. In vitro release profile showed a controlled release of folic acid from the nanoparticles. Treatment of Caco-2 cells with the formulation showed no adverse effects based on MTT and LDH assays, and also, the cellular uptake was significantly higher after 2 h compared to free folic acid. Further, the oral administration of rats with FA-Chi-NPs (1 mg/kg BW) increased the plasma level of both folic acid (3.2-fold) and its metabolites such as tetrahydrofolate (2.3-fold) and 5-methyltetrahydrofolate (1.6-fold) significantly compared to free folic acid. In a bio-distribution study, duodenum and jejunum were found to be the primary sites for absorption. These findings suggest that chitosan may be a promising carrier for the delivery of folic acid and, therefore, could be exploited for various food applications.
    Keywords:  Bioavailability; Chitosan; Folic acid; Nanoencapsulation; Response surface methodology; Transport assay
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.03.042
  15. Expert Opin Drug Deliv. 2022 Mar 12.
       INTRODUCTION: High drug delivery efficiency, desirable therapeutic effects, and low toxicity have become crucial to develop nanotherapeutics. Natural nanoparticles (NPs) from edible plants contain a large quantity of bioactive small molecules, proteins, glycolipids, and microRNAs. The development of these NPs has rapidly attracted increasing attention due to their merits of green production, excellent biocompatibility, anti-inflammatory activities, and anti-tumor capacities.
    AREAS COVERED: Here, we introduce the extraction, purification, and construction strategies of plant-derived exosome-like NPs (PDENs), and expound on their physicochemical properties, biomedical functions, and therapeutic effects against various diseases. We also recapitulate future directions and challenges of this emerging nanotherapeutics.
    EXPERT OPINION: PDENs have been used as natural nanotherapeutics and nanocarriers. The challenges of applying PDENs primarily stem from the lack of understanding of the mechanisms that drive the tissue-specific targeting properties. Elucidating the underlying targeting mechanisms is one of the major focuses in this review, which helps to gain new research opportunities for the development of natural nanotherapeutics. Despite excellent biosafety and therapeutic effects in the treatment of various diseases, the medical translation of these NPs has still been limited by low yields and cold-chain dependence. Therefore, exploiting new techniques will be required for massive production and storage.
    Keywords:  Plant-derived exosome-like nanoparticle; cancer; green production; inflammatory disease; targeted drug delivery
    DOI:  https://doi.org/10.1080/17425247.2022.2053673
  16. Front Chem. 2022 ;10 842682
      The combination of photothermal therapy (PTT) and chemotherapy can remarkably improve the permeability of the cell membrane and reduce the concentration of chemotherapy agents that not only kill the tumor cells effectively but also have adverse effects on normal tissues. It is of great meaning to construct nanomaterials that could be simultaneously applied for tumor eradication with PTT and chemotherapy. In this work, we developed a novel gold nanorod coated with mesoporous organosilica nanoparticles (oMSN-GNR), which presented as an optimal photothermal contrast agent. Moreover, after doxorubicin loading (oMSN-GNR-DOX), the organosilica shell exhibited biodegradable properties under high glutathione in the tumor microenvironment, resulting in massively releasing doxorubicin to kill tumor cells. More importantly, the hyperthermia effect of GNR cores under near-infrared light provided promising opportunities for localized photothermal ablation in vivo. Therefore, the combination of precise chemotherapy and highly effective PTT successfully inhibited tumor growth in liver tumor-bearing mice. This versatile synergistic therapy with local heating and chemotherapeutics precise release opens up the potential clinical application of PTT and chemotherapy therapeutics for malignant tumor eradication.
    Keywords:  GNR; GSH sensitive; chemotherapy; organosilica; photothermal therapy
    DOI:  https://doi.org/10.3389/fchem.2022.842682
  17. Biomater Sci. 2022 Mar 18.
      Chemodynamic therapy (CDT) has received increasing attention due to its unique tumor microenvironment (TME) responsiveness and minimal adverse side effects, but the therapeutic effect of CDT alone is always limited due to the low Fenton or Fenton-like reaction efficiency at tumor sites. Herein, Fe-doped layered double hydroxide (LDH) nanosheets were synthesized to load the anticancer drug epigallocatechin-3-O-gallate (EGCG) and then conjugated with boronic acid-modified hyaluronic acid for targeted and cooperative chemo-chemodynamic therapy of tumors. The formed LDH-EGCG-HA nanoplatforms could specifically target tumor cells overexpressing CD44 receptors, quickly release iron ions and EGCG in the TME, and efficiently generate toxic hydroxyl radicals with the acceleration of Fe3+/Fe2+ cycling in the Fenton reaction by EGCG. The cooperative cancer cell inhibition effect through chemotherapy and chemodynamic therapy was achieved by the significant upregulation of caspase-3 and p53 expression to induce cell apoptosis, and the deactivation of xCT and GPX-4 to inhibit GSH synthesis and reduce lipid peroxides for reinforced ferroptosis. In vivo experiments further verified that the intelligently designed LDH-EGCG-HA nanoplatforms had a superior biocompatibility with normal organs with an excellent inhibition efficacy towards tumors overexpressing CD44 receptors by targeted chemo-chemodynamic therapy.
    DOI:  https://doi.org/10.1039/d2bm00102k
  18. Front Nutr. 2022 ;9 838179
      Cancer, as one of the most life-threatening diseases, has attracted the attention of researchers to develop drugs with minimal side effects. The bioactive macromolecules, such as the polysaccharides, are considered the potential candidates against cancer due to their anti-tumor activities and non-toxic characteristics. The present review provides an overview on polysaccharides' extraction, isolation, purification, mechanisms for their anti-tumor activities, structure-activity relationships, absorption and metabolism of polysaccharides, and the applications of polysaccharides in anti-tumor therapy. Numerous research showed extraction methods of polysaccharides had a significant influence on their activities. Additionally, the anti-tumor activities of the polysaccharides are closely related to their structure, while molecular modification and high bioavailability may enhance the anti-tumor activity. Moreover, most of the polysaccharides exerted an anti-tumor activity mainly through the cell cycle arrest, anti-angiogenesis, apoptosis, and immunomodulation mechanisms. Also, recommendations were made to utilize the polysaccharides against cancer.
    Keywords:  anti-tumor activity; cancer; molecular mechanisms; polysaccharides; structure-activity relationship
    DOI:  https://doi.org/10.3389/fnut.2022.838179
  19. Recent Pat Nanotechnol. 2022 Mar 17.
       BACKGROUND: Novel Drug Delivery Systems (NDDS) provide numerous benefits compared to conventional dosage forms. Poor aqueous solubility, low bioavailability, frequent dosing, and particular hydrophilic lipophilic character of the drug are the biological factors associated with the traditional systems leading to the development of SLNs.
    OBJECTIVE: For improving the solubility profile, enhancing the bioavailability, and attaining the best possible therapeutic effect of lipid inclined or aqueous inclined drug; formulating solid lipid nanoparticles is the best choice.
    METHODS: Solid Lipid Nanoparticles (SLNs) have been projected as a colloidal carrier system having a particle size of 50-1,000 nm, collectively combining the benefits of other colloidal systems like liposomes, emulsions etc. for delivering the drug at the target site. High absorption, high stability, and efficient drug packing enhance the pharmacokinetic and pharmacodynamics properties of the packed drug.
    RESULT: Solid Lipid Nanoparticles can be developed in different dosage forms and administered via routes such as nasal, rectal, oral, topical, vaginal, ocular, and parenteral. They have higher physicochemical stability and the batch size can be easily scaled up at low cost. Lipophilic as well as hydrophilic drugs can be easily incorporated in solid lipid nanoparticles.
    CONCLUSION: In this manuscript, the authors have reviewed different aspects of solid lipid nanoparticles, major principles behind mechanism methods; recent patents, applications, and therapeutic potentials of solid lipid nanoparticles.
    Keywords:  Drug carriers; Drug targeting; Nanocarriers; Nanoformulations.; Nanotechnology; Patents; Solid Lipid Nanoparticles
    DOI:  https://doi.org/10.2174/1872210516666220317143351
  20. IET Nanobiotechnol. 2022 Mar 16.
      Mesoporous magnetic nanoparticles of haematite were synthesised using plant extracts according to bioethics principles. The structural, physical and chemical properties of mesoporous Fe2 O3 nanoparticles synthesised with the green chemistry approach were evaluated by XRD, SEM, EDAX, BET, VSM and HRTEM analysis. Then, their toxicity against normal HUVECs and MCF7 cancer cells was evaluated by MTT assay for 48 h. These biogenic mesoporous magnetic nanoparticles have over 71% of doxorubicin loading efficiency, resulting in a 50% reduction of cancer cells at a 0.5 μg.ml-1 concentration. Therefore, it is suggested that mesoporous magnetic nanoparticles be used as a multifunctional agent in medicine (therapeutic-diagnostic). The produced mesoporous magnetic nanoparticles with its inherent structural properties such as polygonal structure (increasing surface area to particle volume) and porosity with large pore volume became a suitable substrate for loading the anti-cancer drug doxorubicin.
    Keywords:  MCF-7 breast cancer cell line; MTT test; bioethics principles; mesoporous magnetic nanoparticles; targeted transfer
    DOI:  https://doi.org/10.1049/nbt2.12080
  21. Mini Rev Med Chem. 2022 Mar 17.
      Fullerenes are the allotropic form of carbon consisting of a cage-like structure due to which they have attained special attention of the researchers since their discovery in 1985. The unique chemical and physical properties of fullerene have attracted researchers to develop a variety of its biomedical applications. The closed cage structure of fullerenes can be used for various drug delivery applications and can also act as a medium for controlled release formulations. The development of targeted anticancer drug and drug delivery systems is one of the most challenging fields, which is widely studied and researched. In this review, we aim to be comprehensive with a broad interest to the pharmaceutical and biotechnology community to provide the most recent advances on fullerenes as targeted anticancer drug delivery systems with therapeutic applications and challenges.
    Keywords:  Fullerenes; anticancer; antitumor; drug delivery; targeted cytotoxic conjugates; therapeutic applications.
    DOI:  https://doi.org/10.2174/1389557522666220317145544
  22. J Nanobiotechnology. 2022 Mar 18. 20(1): 139
      Ultrasounds are often used in cancer treatment protocols, e.g. to collect tumor tissues in the right location using ultrasound-guided biopsy, to image the region of the tumor using more affordable and easier to use apparatus than MRI and CT, or to ablate tumor tissues using HIFU. The efficacy of these methods can be further improved by combining them with various nano-systems, thus enabling: (i) a better resolution of ultrasound imaging, allowing for example the visualization of angiogenic blood vessels, (ii) the specific tumor targeting of anti-tumor chemotherapeutic drugs or gases attached to or encapsulated in nano-systems and released in a controlled manner in the tumor under ultrasound application, (iii) tumor treatment at tumor site using more moderate heating temperatures than with HIFU. Furthermore, some nano-systems display adjustable sizes, i.e. nanobubbles can grow into micro-bubbles. Such dual size is advantageous since it enables gathering within the same unit the targeting properties of nano bubbles via EPR effect and the enhanced ultrasound contrasting properties of micro bubbles. Interestingly, the way in which nano-systems act against a tumor could in principle also be adjusted by accurately selecting the nano-system among a large choice and by tuning the values of the ultrasound parameters, which can lead, due to their mechanical nature, to specific effects such as cavitation that are usually not observed with purely electromagnetic waves and can potentially help destroying the tumor. This review highlights the clinical potential of these combined treatments that can improve the benefit/risk ratio of current cancer treatments.
    Keywords:  Cancer; Contrast agent; High intensity ultrasounds; Nano-oncology; Nanomaterials; Nanomedicine; Nanotechnology; Sonodynamic therapy; Ultrasound
    DOI:  https://doi.org/10.1186/s12951-022-01243-w
  23. Adv Mater. 2022 Mar 15. e2200449
      Various macro/microscopic biomaterials have been developed for controlled drug delivery in the combination therapy of malignancies. However, uncertain loading ratio, release sequence, and spatiotemporal distribution of drugs hinder their synergistic therapeutic effects and clinical applications. Herein, a tumor microenvironments-adapted composite consisting of thermo-sensitive hydrogel and reactive oxygen species (ROS)-responsive nanogel was developed for precisely sequential drug release to enhance molecular targeted therapy and amplify immune activation. LY3200882 (LY), a selective transforming growth factor-β (TGF-β) inhibitor, was encapsulated in the ROS-responsive nanogel and dispersed uniformly with regorafenib (REG) in a thermo-sensitive hydrogel (Gel/(REG+NG/LY)). After in situ administration, REG was preferentially released from the hydrogel to inhibit tumor growth and promote ROS generation, which triggered the subsequent on-demand release of LY from the nanogel. LY contributed to preventing the epithelial-mesenchymal transition and immune escape of tumor cells induced by elevated TGF-β. In subcutaneous and orthotopic colorectal tumor-bearing mouse models, Gel/(REG+NG/LY) effectively inhibited tumor growth and liver metastasis by increasing the tumor infiltration of CD8+ T cells, reducing the recruitment of tumor-associated macrophages and myeloid-derived suppressor cells, and promoting the polarization of macrophages from M2 to M1 type, indicating the significant potential in improving the prognosis of advanced cancer patients. This article is protected by copyright. All rights reserved.
    Keywords:  polypeptide; reactive oxygen species-responsive nanogel; sequential drug delivery; synergistic cancer therapy; thermo-sensitive hydrogel
    DOI:  https://doi.org/10.1002/adma.202200449
  24. J Colloid Interface Sci. 2022 Mar 03. pii: S0021-9797(22)00364-2. [Epub ahead of print]617 315-325
      Metallodrug platinum compounds are indispensable components in the current standard combination for colorectal cancer treatment yet with severe additional adverse effects compromising the clinical outcomes. Having tumor microenvironment modulation and immunostimulatory effect, bio-compatible manganese (Mn) materials hold great promise for developing alternate metallodrug combination treatments. In this research, a novel MnO2-shelled nanoplatform was constructed to load two FDA-approved anti-tumor drugs, i.e., immunomodulatory curcumin (Cur) and immunostimulatory doxorubicin (Dox) to achieve enhanced dual-chemotherapy of primary tumors and remarkable inhibition of distant colorectal tumors. The experimental results have shown that MnO2 efficiently enhanced Dox/Cur chemotherapy with significant primary tumor inhibition (81%) at very low dosages (5.0 and 1.0 mg/kg of Cur and Dox, respectively). Furthermore, the MnO2-assisted Dox/Cur chemotherapy promoted strong tumoricidal adaptive immune responses and overwhelmingly inhibited tumorigenesis in the tumor rechallenge experiment. This work has thus demonstrated the promising efficacy of the Mn/Dox/Cur nano-formulation and provided a novel way to improve immunostimulation of conventional chemotherapeutics using active metal oxide nanomaterials for colorectal cancer treatment.
    Keywords:  Colorectal cancer combination treatment; Curcumin; Doxorubicin; Immunostimulatory nanomedicine; MnO(2)
    DOI:  https://doi.org/10.1016/j.jcis.2022.02.132
  25. Pharm Dev Technol. 2022 Mar 17. 1-47
      In the last few decades, the interest in biodegradable materials for biomedical applications has increased significantly. Both natural and synthetic biodegradable polymers (BDPs) have been broadly explored for various biomedical applications. These include sutures and wound dressings, screws for bone fracture, scaffolds in tissue engineering, implants, and other carriers for targeted and sustained release drug delivery. Owing to their unique characteristics, including their surface charge variable copolymer block and composition and film-forming properties, BDPs have been widely used as favourable materials for ophthalmic drug delivery. Mucoadhesive BDPs have been used in ophthalmic formulations to prolong drug retention time and improve bioavailability, allowing ophthalmic controlled release systems to design. Furthermore, BDPs-based implants, microneedles, and injectable nano- and micro-particles enabled ocular posterior segment targeting and, most importantly, circumvented the need for removing the delivery systems after application. This review outlines the major advances of BDPs and highlights the latest progress of employing natural and synthetic BDPs for various biomedical applications, emphasising the treatment and management of ophthalmic conditions.
    Keywords:  Biodegradable polymers (BDPs); Hydrogel; Implant; Natural and synthetic BDPs; Ocular patents; Ophthalmic application
    DOI:  https://doi.org/10.1080/10837450.2022.2055063
  26. Beilstein J Nanotechnol. 2022 ;13 284-291
      Oxidative stress can lead to permanent and irreversible damage to cellular components and even cause cancer and other diseases. Therefore, the development of antioxidative reagents is an important strategy to alleviate chronic diseases and maintain the redox balance in cells. Small-molecule bioactive compounds have exhibited huge therapeutic potential as antioxidants and anti-inflammatory agents. Myricetin (Myr), a well-known natural flavonoid, has drawn wide attention because of its high antioxidant, anti-inflammatory, antimicrobial, and anticancer efficacy. Especially regarding antioxidation, Myr is capable of not only chelating intracellular transition metal ions for removing reactive oxygen species, but also of activating antioxidant enzymes and related signal pathways and, thus, of sustainably scavenging radicals. However, Myr is poorly soluble in water, which limits its bioavailability for biomedical applications, and even its clinical therapeutic potential. The antioxidant peptide glutathione (GSH) plays a role as antioxidant in cells and possesses good hydrophilicity and biocompatibility. However, it is easily metabolized by enzymes. To take advantages of their antioxidation activity and to overcome the abovementioned limitations, GSH, Zn2+, and Myr were selected to co-assemble into Myr-Zn2+-GSH nanoparticles or nanoarchitectonics. This study offers a new design to harness stable, sustainable antioxidant nanoparticles with high loading capacity, high bioavailability, and good biocompatibility as antioxidants.
    Keywords:  antioxidant; co-assembly; glutathione; myricetin; nanoarchitectonics
    DOI:  https://doi.org/10.3762/bjnano.13.23
  27. Bioconjug Chem. 2022 Mar 16.
      We present the synthesis of amorphous, mesoporous, colloidal magnesium phosphate-citrate nanoparticles (MPCs) from biogenic precursors, resulting in a biocompatible and biodegradable nanocarrier that amplifies the action of the anticancer drug methotrexate (MTX). Synthesis conditions were gradually tuned to investigate the influence of the chelating agent citric acid on the colloidal stability and the mesoporosity of the obtained nanoparticles. With optimized synthesis conditions, a large BET surface area of 560 m2/g was achieved. We demonstrate the potential of these biocompatible and biodegradable mesoporous MPCs as a drug delivery system. Lipid-coated MPCs were used to load the fluorescent dye calcein and the chemotherapeutic agent MTX into the mesopores. In vitro experiments show very low premature release of the cargo but efficient stimuli-responsive release in an environment of pH 5.5, in which MPCs degrade. Lipid-coated MPCs are taken up by cancer cells and are nontoxic up to concentrations of 100 μg/mL. When loaded with MTX serving as a representative model drug for in vitro studies, MPCs induced efficient cell death with an IC50 value of 1.1 μg/mL. Compared to free MTX, its delivery with MPCs enhances its efficiency by an order of magnitude. In summary, we have developed a biodegradable nanomaterial synthesized from biocompatible precursors that are neither toxic by themselves nor in the form of nanoparticles. With these features, MPCs may be applied as drug delivery systems and have the potential to reduce the side effects of current chemotherapies.
    DOI:  https://doi.org/10.1021/acs.bioconjchem.1c00565
  28. Front Immunol. 2022 ;13 845923
      Although immunotherapy has achieved good results in various cancer types, a large proportion of patients are limited from the benefits. Hypoxia and metabolic reprogramming are the common and critical factors that impact immunotherapy response. Here, we present current research on the metabolism reprogramming induced by hypoxia on antitumor immunity and discuss the recent progression among preclinical and clinical trials exploring the therapeutic effects combining targeting hypoxia and metabolism with immunotherapy. By evaluating the little clinical translation of the combined therapy, we provide insight into "understanding and regulating cellular metabolic plasticity under the current tumor microenvironment (TME)," which is essential to explore the strategy for boosting immune responses by targeting the metabolism of tumor cells leading to harsh TMEs. Therefore, we highlight the potential value of advanced single-cell technology in revealing the metabolic heterogeneity and corresponding phenotype of each cell subtype in the current hypoxic lesion from the clinical patients, which can uncover potential metabolic targets and therapeutic windows to enhance immunotherapy.
    Keywords:  cancer immunotherapy; cell subtypes; hypoxia; metabolic reprogramming; single-cell analysis
    DOI:  https://doi.org/10.3389/fimmu.2022.845923
  29. Nanoscale. 2022 Mar 16.
      Glioblastoma (GBM) is the most lethal primary intracranial tumor because of its high invasiveness and recurrence. Therefore, nanocarriers with blood-brain barrier (BBB) penetration and transcranial-controlled drug release and activation are rather attractive options for glioblastoma treatment. Herein, we designed a multifunctional nanocarrier (T-TKNPVP) that combined targeted X-ray-induced photodynamic therapy (X-PDT) and cascaded reactive oxygen species (ROS)-boosted chemotherapy. The T-TKNPVP loaded with verteporfin (VP) and paclitaxel (PTX) was self-assembled from an angiopep-2 (Ang) peptide, functionalized Ang-PEG-DSPE and ROS-sensitive PEG-TK-PTX conjugate. After systemic injection, the T-TKNPVP efficiently crossed the BBB and targeted the GBM cells via receptor-mediated transcytosis. Upon X-ray irradiation, they can generate a certain amount of ROS, which not only induces X-PDT but also locoregionally activates PTX release and action by cleaving the TK bridged bonds. As evidenced by 9.4 T MRI and other experiments, such nanocarriers offer significant growth inhibition of GBM in situ and prolong the survival times of U87-MG tumor-bearing mice. Taken together, the designed T-TKNPVP provided an alternative avenue for realizing transcranial X-PDT and X-ray-activated chemotherapy for targeted and locoregional GBM treatment in vivo.
    DOI:  https://doi.org/10.1039/d2nr00436d
  30. ACS Appl Mater Interfaces. 2022 Mar 14.
      Chemodynamic therapy (CDT) has attracted increasing attention in tumor treatment but is limited by insufficient endogenous H2O2. Moreover, it is challenging for monotherapy to achieve a satisfactory outcome due to tumor complexity. Herein, we developed an intelligent nanoplatform that could respond to a tumor microenvironment to induce efficient CDT without complete dependence on H2O2 and concomitantly generate chemotherapy and oncosis therapy (OT). The nanoplatform was constructed by a calcium- and iron-doped mesoporous silica nanoparticle (CFMSN) loaded with dihydroartemisinin (DHA). After entering into cancer cells, the nanoplatform could directly convert the intracellular H2O2 into toxic •OH due to the Fenton-like activity of CFMSN. Meanwhile, the acidic microenvironment and endogenous chelating molecules triggered Ca2+ and Fe3+ release from the nanoplatform, causing particle collapse with accompanying DHA release for chemotherapy. Simultaneously, the released Ca2+ induced intracellular Ca2+-overloading for OT, which was further enhanced by DHA, while the released Fe3+ was reduced to reactive Fe2+ by intracellular glutathione, guaranteeing efficient Fenton reaction-mediated CDT. Moreover, Fe2+ cleaved the peroxy bonds of DHA to generate C-centered radicals to further amplify CDT. Both in vitro and in vivo results confirmed that the nanoplatform exhibited excellent anticancer efficacy via the synergistic effect of multi therapeutic modalities, which is extremely promising for high-efficient cancer therapy.
    Keywords:  calcium; cancer therapy; iron; mesoporous silica; nanoplatform
    DOI:  https://doi.org/10.1021/acsami.2c01913
  31. Adv Mater. 2022 Mar 15. e2201200
      Nanoparticles (NPs)-based cancer therapeutics is generally impeded by poor drug penetration into solid tumors due to their dense tumor extracellular matrix (ECM). Herein, we develop pH/redox-responsive dendritic polymer-based NPs to amplify the neighboring effect for improving drug penetration and driving cell apoptosis via combination therapy. Pyropheophorbide a (Ppa) is conjugated with PEGylated dendritic peptides via disulfide bonds and doxorubicin (DOX) encapsulated in the conjugate to construct dual-responsive NPs, PDPP@D. Delayed released DOX and Ppa from PDPP@D exert their combination therapeutic effect to induce cell apoptosis, and then they are liberated out of dying cells to amplify the neighboring effect, resulting in their diffusion through the dense ECM and penetration into solid tumors. Transcriptome studies reveal that PDPP@D leads to irreversible stress on the endoplasmic reticulum and inhibits cell protection through blocking the IRE1-dependent survival pathway and unleashing the DR5-mediated caspase activity to promote cell death. The strategy of amplifying the neighboring effect of NPs through combination therapy may offer great potential in enhancing drug penetration and eradicating solid tumors. This article is protected by copyright. All rights reserved.
    Keywords:  combination therapy; drug delivery; drug penetration; endoplasmic reticulum stresses; neighboring effect
    DOI:  https://doi.org/10.1002/adma.202201200
  32. Eur J Pharm Biopharm. 2022 Mar 10. pii: S0939-6411(22)00050-9. [Epub ahead of print]
      Cancer immunotherapy, which harnesses the host immune system to identify, attack, and remove tumor cells, has emerged as one of the most promising cancer therapies. Nevertheless, the further applications of clinic-approved immunotherapies have been hindered due to their low response rates and adverse reactions. Recently, photodynamic therapy (PDT)-based photonanomedicines (PNMs) have gained much attention as they have been reported to participate in immunotherapy by triggering the death of immunogenic tumor cells. This contributes to the initiation of the immune response and the infiltration of toxic T lymphocytes, thereby eliminating metastatic tumor cells. When combined with conventional immunotherapy, such immunostimulatory properties of PNMs offer opportunities to enhance anti-cancer immunity. This review elaborates on the latest strategies for PNMs to enhance the anti-cancer efficiency of immunotherapy, with emphasis on PNM-synergized immunotherapy, PNM-based nano-drug delivery systems in synergistic immunotherapy and PNM-based improved infiltration of toxic T lymphocytes in synergistic immunotherapy. Moreover, the current challenges and prospective developments for PNM-synergized immunotherapy to realize the transition from bench to bedside are also discussed.
    Keywords:  Cancer therapy; Delivery system; Nanomedicine; Photodynamic immunotherapy
    DOI:  https://doi.org/10.1016/j.ejpb.2022.03.002
  33. Nano Lett. 2022 Mar 14.
      Uncontrolled growth of tumor cells is highly dependent on the energy metabolism. Fasting-mimicking diet (FMD) is a low-calorie, low-protein, low-sugar diet representing a promising strategy for cancer treatment. However, triglyceride stored in adipose tissue is hydrolyzed into free fatty acids and glycerol for energy supply during FMD treatment. Herein, we design a nutrient-sensing nanodrug, VFETX, which is self-assembled with vitamin B1 (VB1), ferrous ions, and etomoxir (ETX). FMD treatment upregulate the expression of VB1 transporters on tumor cells, thereby increasing cellular uptake and tumor accumulation of VFETX. Importantly, treatments of VFETX and FMD synergistically inhibit the energy metabolism in tumor cells and subsequently markedly enhance cytotoxicity of ETX. As a result, VFETX nanodrugs efficiently inhibit the growth of two tumor models in vivo without obvious side effects. This study demonstrates the potential of FMD-assisted nutrient-sensing nanodrugs for cancer therapy.
    Keywords:  Biomolecule; cancer therapy; fasting-mimicking diet; self-assembly
    DOI:  https://doi.org/10.1021/acs.nanolett.2c00356
  34. Biomed Pharmacother. 2022 Apr;pii: S0753-3322(22)00158-5. [Epub ahead of print]148 112770
      Traumatic brain injury (TBI) affects approximately 50% of the world population at some point in their lifetime. To date, there are no effective treatments as most of the damage occurs due to secondary effects through a variety of pathophysiological pathways. The phytoceutical curcumin has been traditionally used as a natural remedy for numerous conditions including diabetes, inflammatory diseases, and neurological and neurodegenerative disorders. We have carried out a system pharmacology study to identify potential targets of a difluorinated curcumin analogue (CDF) that overlap with those involved in the pathophysiological mechanisms of TBI. This resulted in identification of 312 targets which are mostly involved in G protein-coupled receptor activity and cellular signalling. These include adrenergic, serotonergic, opioid and cannabinoid receptor families, which have been implicated in regulation of pain, inflammation, mood, learning and cognition pathways. We conclude that further studies should be performed to validate curcumin as a potential novel treatment to ameliorate the effects of TBI.
    Keywords:  CDF; Curcumin-difluorinated; Inflammation; Molecular target prediction; TBI; Traumatic brain injury
    DOI:  https://doi.org/10.1016/j.biopha.2022.112770
  35. Front Oncol. 2022 ;12 812534
      Ferroptosis is a new form of programmed cell death (PCD) characterized by an excess iron accumulation and subsequent unbalanced redox states. Ferroptosis is different from the already reported PCD and has unique morphological features and biochemical processes. Ferroptosis was first elaborated by Brent R. Stockwell's lab in 2012, in which small molecules erastin and RSL-3 induce PCD in Ras mutant cell lines. Ferroptosis involves various physiological processes and occurrence of disease and especially shows strong potential in cancer treatment. Development of small molecule compounds based on Stockwell's research was found to kill cancer cells, and some FDA-approved drugs were discovered to result in ferroptosis of cancer cells. Radiotherapy and checkpoint therapy have been widely used as a treatment for many types of cancer. Recently, some papers have reported that chemotherapy, radiotherapy, and checkpoint therapy induce ferroptosis of cancer cells, which provides new strategies for cancer treatment. Nevertheless, the limitless proliferation of tumor cells and the lack of cell death mechanisms are important reasons for drug resistance for tumor therapy. Therefore, we reviewed the molecular mechanism of ferroptosis and sensitivity to ferroptosis of different cancer cells and tumor treatment strategy.
    Keywords:  cancers; drug resistance; ferroptosis; metabolism; tumor treatment
    DOI:  https://doi.org/10.3389/fonc.2022.812534
  36. Crit Rev Food Sci Nutr. 2022 Mar 15. 1-32
      Epidemiological studies have shown that consumption of green tea, coffee, wine, and curry may contribute to a reduced risk of various cancers. However, there are some cancer site-specific differences in their effects; for example, the consumption of tea or wine may reduce bladder cancer risk, whereas coffee consumption may increase the risk. Animal and cell-based experiments have been used to elucidate the anticancer mechanisms of these compounds, with reactive oxygen species (ROS)-based mechanisms emerging as likely candidates. Chlorogenic acid (CGA), curcumin (CUR), epigallocatechin gallate (EGCG), and resveratrol (RSV) can act as antioxidants that activate AMP-activated protein kinase (AMPK) to downregulate ROS, and as prooxidants to generate ROS, leading to the downregulation of NF-κB. Polyphenols can modulate miRNA (miR) expression, with these dietary polyphenols shown to downregulate tumor-promoting miR-21. CUR, EGCG, and RSV can upregulate tumor-suppressing miR-16, 34a, 145, and 200c, but downregulate tumor-promoting miR-25a. CGA, EGCG, and RSV downregulate tumor-suppressing miR-20a, 93, and 106b. The effects of miRs may combine with ROS-mediated pathways, enhancing the anticancer effects of these polyphenols. More precise analysis is needed to determine how the different modulations of miRs by polyphenols relate to the cancer site-specific differences found in epidemiological studies related to the consumption of foods containing these polyphenols.
    Keywords:  anticancer effects; chlorogenic acid; curcumin; epigallocatechin gallate; microRNA; resveratrol
    DOI:  https://doi.org/10.1080/10408398.2022.2038540
  37. Mikrochim Acta. 2022 Mar 18. 189(4): 150
      This study investigated, for the first time, the antimicrobial properties of polyethylene glycol-functionalized poly(N-phenylglycine) nanoparticles (PNPG-PEG NPs). PNPG-PEG NPs exhibit high extinction coefficient in the near-infrared (NIR) region; they can convert light energy into heat energy with high thermal transformation efficiency. Additionally, they can generate cytotoxic reactive oxygen species (ROS) upon light irradiation. Also, PNPG-PEG NPs are not cytotoxic. All these properties make them appropriate for combined dual-modal photothermal and photodynamic therapies. The antibacterial activity of PNPG-PEG NPs was assessed using Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) pathogenic strains. The results revealed that NIR light (810 nm) irradiation for 10 min could kill effectively the planktonic bacteria and destroy Escherichia coli and Staphylococcus aureus biofilms. The results demonstrated that PNPG-PEG NPs represent a very effective nanoplatform for killing of pathogenic bacteria.
    Keywords:  Antibacterial therapy; Biofilm; Escherichia coli; Polymer-based nanomaterials; Staphylococcus aureus
    DOI:  https://doi.org/10.1007/s00604-022-05181-0
  38. Phytother Res. 2022 Mar 18.
      Systemic autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus represent various autoimmune conditions identified by immune system dysregulation. The activation of immune cells, auto-antigen outbreak, inflammation, and multi-organ impairment is observed in these disorders. The immune system is an essential complex network of cells and chemical mediators which defends the organism's integrity against foreign microorganisms, and its precise operation and stability are compulsory to avoid a wide range of medical complications. Curcumin is a phenolic ingredient extracted from turmeric and belongs to the Zingiberaceae, or ginger family. Curcumin has multiple functions, such as inhibiting inflammation, oxidative stress, tumor cell proliferation, cell death, and infection. Nevertheless, the immunomodulatory influence of curcumin on immunological reactions/processes remains mostly unknown. In the present narrative review, we sought to provide current information concerning the preclinical and clinical uses of curcumin in systemic autoimmune diseases.
    Keywords:  curcumin; immunomodulatory effect; inflammation; systemic autoimmune diseases
    DOI:  https://doi.org/10.1002/ptr.7417
  39. J Mater Chem B. 2022 Mar 18.
      Polyprodrugs with drugs as the structural units have been recognized as promising drug self-delivery systems (DSDSs) for tumor chemotherapy, especially ones in which the drug structural units are linked with both pH- and reduction-cleavable conjugations. However, stable DOX derivatives are released after the acid/reduction co-triggered degradation, exhibiting low antitumor efficacy due to their low solubility. Herein, a novel acid/reduction co-triggered degradable amphiphilic copolyprodrug was designed via the facile polycondensation of an acid-labile dimer (D-DOXADH) and disulfide-containing monomer (DNC) with a PEGylated dimer (D-DOXADH-PEG) as an end-capping reagent. The resultant amphiphilic copolyprodrug (PDOXSS-ADH-PEG) with a high DOX content of 61.1% could easily self-assemble into nanoparticles around 154 nm in size, possessing excellent acid/reduction co-triggered DOX release and enhanced inhibition of tumor growth compared to free DOX towards HepG2 cells but showed good cytocompatibility towards L02 cells.
    DOI:  https://doi.org/10.1039/d2tb00150k
  40. J Biomater Sci Polym Ed. 2022 Mar 16. 1-36
      Skin-cancer (SC) is more common than all other cancers affecting large percentage of the population in the world and is increasing in terms of morbidity and mortality. In the United States, 3million people are affected by SC annually whereas millions of people are affected globally. Melanoma is fifth most common cancer in the United States. SC is commonly occurred in white people as per WHO. SC is divided into two groups i.e. melanoma and non-melanoma. In the previous two decades, management of cancer remains to be a tough and a challenging task for many scholars. Presently, the treatment protocols are mostly based on surgery and chemo-radiation therapy, which sooner or later harm the unaffected cells too. To reduce these limitations, nano scaled materials and its extensive range may be recognized as the probable carriers for the selective drug delivery in response to cancerous cells. Recently, the nanocarriers based drugs and their combinations were found to be a new and interesting approach of study for the management of skin carcinoma to enhance the effectiveness, to lessen the dose-dependent side effects and to avoid the drug resistance. This review may emphasize on the wide-range of information on nanotechnology-based drugs and their combination with physical techniques.
    Keywords:  combination drug delivery; drug delivery; drug resistance; nanomedicine; nanotechnology; skin cancer; toxicity
    DOI:  https://doi.org/10.1080/09205063.2022.2054399
  41. J Food Sci. 2022 Mar 12.
      Coriandrum sativum (coriander) is an edible herb in the family Apiaceae. The leaves, fruits, and stems of C. sativum have long been used as culinary spice due to their favorable odor. Traditional practitioners used this plant for treating different diseases like blepharitis, scabies, aphthous stomatitis, laryngitis, headache, and palpitation. In modern researches, coriander has demonstrated anxiolytic, anticonvulsant, antimigraine, neuroprotective, analgesic, diuretic, hypoglycemic, hypolipidemic, hypotensive, anticancer, and antioxidant activities. Coriander contains a wide range of bioactive phytochemicals among which phenylpropenes, terpenoids, isocoumarins, phytosterols, and fatty acids are the most important. This review provides information about the botanical and ethnobotanical aspects, chemical profile, therapeutic uses in Islamic traditional medicine (ITM), and recent pharmacological studies of coriander effects. The results have shown that coriander and its monoterpenoid compound, linalool, can be considered as potential drug candidates for treating metabolic syndrome and different inflammatory conditions especially neural and CNS diseases.
    Keywords:  Apiaceae; Coriandrum sativum; coriander; functional foods; traditional medicine
    DOI:  https://doi.org/10.1111/1750-3841.16085
  42. Anticancer Agents Med Chem. 2022 Mar 17.
      Global efforts invested for the prevention and treatment of cancer need to be repositioned to develop safe, effective, and economic anticancer therapeutics by adopting rational approaches of drug discovery. Drug repurposing is one of the established approaches to reposition old, clinically approved off patent noncancer drugs with known targets into newer indications. The literature review suggests key role of drug repurposing in the development of drugs intended for cancer as well as noncancer therapeutics. A wide category of noncancer drugs namely, drugs acting on CNS, anthelmintics, cardiovascular drugs, antimalarial drugs, anti-inflammatory drugs have come out with interesting outcomes during preclinical and clinical phases. In the present article a comprehensive overview of the current scenario of drug repurposing for the treatment of cancer has been focused. The details of some successful studies along with examples have been included followed by associated challenges.
    Keywords:  Anticancer drugs; Cancer therapeutics; Drug discovery; Drug repurposing; Multitargeting; Non-cancer drugs
    DOI:  https://doi.org/10.2174/1871520622666220317140557
  43. Front Med (Lausanne). 2022 ;9 795762
      Aldehyde dehydrogenases (ALDHs) are a family of detoxifying enzymes often upregulated in cancer cells and associated with therapeutic resistance. In humans, the ALDH family comprises 19 isoenzymes active in the majority of mammalian tissues. Each ALDH isoform has a specific differential expression pattern and most of them have individual functional roles in cancer. ALDHs are overexpressed in subpopulations of cancer cells with stem-like features, where they are involved in several processes including cellular proliferation, differentiation, detoxification and survival, participating in lipids and amino acid metabolism and retinoic acid synthesis. In particular, ALDH enzymes protect cancer cells by metabolizing toxic aldehydes in less reactive and more soluble carboxylic acids. High metabolic activity as well as conventional anticancer therapies contribute to aldehyde accumulation, leading to DNA double strand breaks (DSB) through the generation of reactive oxygen species (ROS) and lipid peroxidation. ALDH overexpression is crucial not only for the survival of cancer stem cells but can also affect immune cells of the tumour microenvironment (TME). The reduction of ROS amount and the increase in retinoic acid signaling impairs immunogenic cell death (ICD) inducing the activation and stability of immunosuppressive regulatory T cells (Tregs). Dissecting the role of ALDH specific isoforms in the TME can open new scenarios in the cancer treatment. In this review, we summarize the current knowledge about the role of ALDH isoforms in solid tumors, in particular in association with therapy-resistance.
    Keywords:  aldehyde dehydrogenase; cancer stem cell; double strand brakes (DSB); immunosuppression; therapeutic resistance
    DOI:  https://doi.org/10.3389/fmed.2022.795762
  44. Curr Pharm Des. 2022 Mar 17.
      Quercetin is the main dietary flavonoid with a wide range of pharmacological activities. However, the poor gastrointestinal absorption and low bioavailability of quercetin curtails its clinical applications.. Enhancement the bioavailability of quercetin focuses on the application of delivery systems technologies such as microparticle delivery systems, solid dispersions, encapsulation, phospholipid complexes, and hydrogels , which have been systematically reviewed .And theirapplications in vitro and in vivo animal experiments also been described, promoting the development and optimization of drug delivery system for clinical applications.
    Keywords:  hydrogels; nanoparticles delivery systems; phospholipid complexes; quercetin; review; solid dispersions
    DOI:  https://doi.org/10.2174/1381612828666220317141923
  45. Front Pharmacol. 2022 ;13 807498
      Chemotherapy, as one of the principal modalities for cancer therapy, is limited by its non-specific and inefficient delivery to tumors. To overcome these limitations, we report herein a dual-targeted aptamer-decorated DNA hydrogel system (DTA-H) to achieve efficient, stable, and targeted delivery of drugs. Firstly, DNA hydrogel was formed by the rolling circle amplification. By reasonable design, double target and multivalent aptamers were decorated on DNA hydrogel to load DOX. The results confirmed that DTA-H can deliver chemotherapy drugs and aptamer nucleic acids drugs to target cells, inducing degradation of HER2 protein while chemotherapy is synergistic to inhibit HER2-positive breast cancer growth. The proposed drug delivery system has significant potential to achieve efficient, stable, and targeted delivery of drugs and cancer therapy.
    Keywords:  DNA hydrogel; aptamer; doxorubicin; synergistic therapy; targeted drug delivery
    DOI:  https://doi.org/10.3389/fphar.2022.807498
  46. ACS Appl Mater Interfaces. 2022 Mar 17.
      Incomplete local treatment of solid tumors is the main cause of tumor difficult to cure, and easily leads to tumor metastasis and recurrence. The dense external matrix and hypoxic microenvironment of solid tumors severely restrict the therapy efficacy of local tumors. Enhancing the infiltration ability of agents to tumor tissues and adapting the therapy mode favored to hypoxic microenvironments are beneficial to improve the cure rate of tumors. In this work, we designed and developed a self-assembled biomaterial with a cascade effect triggered by near-infrared light. The self-assembly was combined of biotin, phase change material (PNIPAM), photochemical agent (ATT-2), and alkyl radical generator (AIPH). In the assembly, biotin acted as a targeted group. ATT-2 was used to provide heat to synergistically induce the phase change and decompose alkyl radicals. The superficial and deep tumors were ablated by heat and alkyl radicals with white light irradiation of the assembly, respectively. The assay in vivo showed that the self-assembly could effectively eliminate local lesions of solid tumors. This work provides new insights for improving the cure rate of tumors, which not only develops biomaterials adapted to the tumor microenvironment, but also proposes new therapies for complete elimination of solid tumors.
    Keywords:  alkyl radicals; biomaterial; photothermal therapy; self-assembly; solid tumors
    DOI:  https://doi.org/10.1021/acsami.2c00448
  47. Pharmacol Res. 2022 Mar 10. pii: S1043-6618(22)00120-7. [Epub ahead of print]178 106175
      Obesity is a significant public health problem worldwide that is characterized by abnormal or excessive fat accumulation. Unfortunately, the application of available weight-loss drugs has been restricted because of their serious adverse effects. Browning of white adipose tissue (WAT), which refers to the transformation of white adipocytes to beige adipocytes under certain stimulations, is regarded as a new strategy to solve the obesity problem. Numerous studies have recently evidenced that traditional Chinese medicine (TCM) could promote browning of WAT with multi-component and multi-target characteristics. This article summarizes natural constituents from TCM with stimulatory effects on browning of WAT in the past two decades. The active ingredients can be generally divided into polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids and others, such as resveratrol, quercetin, curcumin, genistein, capsaicin, epigallocatechin gallate (EGCG), berberine, menthol, emodin and ginsenosides. Simultaneously, the chemical structures, source, model, efficacy and mechanism of these monomeric compounds are also described. And the mechanisms of these active ingredients are mainly involved in the regulation of PRDM16, PGC-1α, PPARγ, SIRT1, AMPK, β3-adrenergic receptors, TRPV1 and TRPM8 channels, FGF21 and miRNAs. The present article opens opportunities for developing novel drugs or supplements from TCM with wide acceptability to prevent obesity progression and its associated metabolic disorders.
    Keywords:  Beige adipocytes; Berberine (PubChem CID: 2353); Browning of white adipose tissue; Capsaicin (PubChem CID: 1548943); Curcumin (PubChem CID: 969516); Emodin (PubChem CID: 3220); Epigallocatechin gallate (PubChem CID: 65064); Genistein (PubChem CID: 5280961); Ginsenoside Rb1 (PubChem CID: 9898279); Menthol (PubChem CID: 1254); Natural products; Obesity; Quercetin (PubChem CID: 5280459); Resveratrol (PubChem CID: 445154); Traditional Chinese medicine
    DOI:  https://doi.org/10.1016/j.phrs.2022.106175
  48. Curr Cardiol Rev. 2022 ;18(1): 89-100
       BACKGROUND: The present investigation was designed to systematically review the antihypertensive effects of all the organic and inorganic nanoparticles in the in vitro, in vivo, and clinical trials.
    METHODS: The current study was carried out using 06-PRISMA guideline and registered in the CAMARADES- NC3Rs Preclinical Systematic Review and Meta-analysis Facility (SyRF) database. The search was performed on five English databases, including Scopus, PubMed, Web of Science, EMBASE, and Google Scholar, without time limitation for publications worldwide related to the anti-hypertensive effects of all the organic and inorganic nanoparticles without date limitation, so as to identify all the published articles (in vitro, in vivo, clinical, and case-control). Studies in any language were entered in the search step if they had an English abstract.
    RESULTS: Out of 3602 papers, 60 including 25 werein vitro (41.7%), 17 in vitro / in vivo (28.3%), 16 in vivo (26.7%), and 2 in vitro / ex vivo (3.3%) up to 2020 met the inclusion criteria for discussion in this systematic review. The most widely used nanoparticles were organic nanoparticles such as polylactic acid, poly lactic-co-glycolic acid (PLGA), lipid, chitosan, etc., followed by inorganic nanoparticles such as silver and palladium nanoparticles.
    CONCLUSION: This review demonstrated the anti-hypertensive effects of some organic and inorganic nanoparticles alone or in combination with the available anti-hypertensives. We found that organic nanoparticles such as PGLA and chitosan can be considered as preferred options in nanomedicine for treating high blood pressure. The results also showed these nanoparticles displayed antihypertensive effects through some mechanisms such as sustained release forms via increasing bioavailability, increasing oral bioavailability and improving oral and non-oral absorption, counteracting excessive superoxide, decreasing blood pressure, etc. However, further investigations are required to prove these effects, particularly in clinical settings, as well as their accurate possible mechanisms and toxicity.
    Keywords:  Hypertension; PGLA; blood pressure; lipid nanoparticles; metal nanoparticles; polymeric nanoparticles
    DOI:  https://doi.org/10.2174/1573403X17666210611115823
  49. Phytomedicine. 2022 Mar 03. pii: S0944-7113(22)00093-9. [Epub ahead of print]99 154015
       BACKGROUND: Breast cancer is one of the malignant tumors with the highest morbidity and mortality rate. Numerous efficient anti-breast cancer drugs are being derived from the development of natural products. Voacamine (VOA), a bisindole alkaloid isolated from Voacanga africana Stapf, possesses various pharmacological and biological activities.
    PURPOSE: In this study, we investigated the efficacy of VOA against breast cancer cells and elucidated the underlying mechanisms in vitro and in vivo.
    METHODS: Human breast cancer cell line MCF-7 and mouse breast cancer cell line 4T1 were used to study the underlying anti-cancer mechanisms of VOA. The proliferation was detected by MTT, colony formation, cell proliferation and wound-healing migration assays. Flow cytometry was utilized to determine the level of reactive oxygen species (ROS) cell-cycle, apoptosis and mitochondrial membrane potential. The target proteins were analyzed by Western blot. Molecular docking was performed and scored by AutoDock. Subcutaneous cancer models in mice were established to evaluate the anticancer effects in vivo.
    RESULT: Our results demonstrated that VOA selectively suppressed breast cancer MCF-7 and 4T1 cells proliferation with IC50 values of 0.99 and 1.48 μM, and significantly inhibited the migration and colony formation of tumor cells. Furthermore, the cell cycle was arrested in the S phase with the decreased expression levels of CDK2, Cyclin A and Cyclin E. Additionally, exposure to VOA dose-dependently brought about dose-dependently the loss of mitochondrial membrane potential (Δψm) and amassment of reactive oxygen species (ROS), resulting in the initiation of the intrinsic apoptotic pathway. Western blot analysis unveiled that VOA significantly activated mitochondrial-associated apoptosis and obviously suppress the PI3K/Akt/mTOR pathway via modulation of related protein expression levels in both tumor cell lines. In tumor-bearing mouse models, administration of VOA dose-dependently inhibited the tumor growth without causing apparent toxicities.
    CONCLUSION: These findings revealed the novel properties of VOA in promoting apoptosis of breast cancer cells by activating mitochondrial-associated apoptosis signaling pathway and inhibiting PI3K/Akt/mTOR signaling pathway and significantly decreasing tumor size without detecting appreciable toxicity. In summary, the present results demonstrated VOA could be an encouraging drug candidate to cure breast cancer, exhibiting an effective method to exploit unique drugs from natural components.
    Keywords:  PI3K/Akt/mTOR; Voacamine (VOA); apoptosis; breast cancer; mitochondrial membrane potential; reactive oxygen species
    DOI:  https://doi.org/10.1016/j.phymed.2022.154015
  50. Colloids Surf B Biointerfaces. 2022 Mar 10. pii: S0927-7765(22)00139-4. [Epub ahead of print]214 112456
      Photodynamic therapy (PDT), a non-invasive and safe treatment, is a clinical promising alternative strategy for certain cancers. Although PDT can trigger tumor specific immunity, the immunosuppressive tumor microenvironment severely limits the efficacy of photodynamic immunotherapy. Curcumol (CUR), extracted from essential oils of traditional Chinese medicine, has potential immune activation effect for cancer immunotherapy. Considering the fat solubility and volatility hinder the in vivo application of essential oils, a metal-organic framework system (Named as CuTPyP/F68) composed of porphyrin and Cu2+ was constructed for delivering CUR (Named as CUR@CuTPyP/F68). The in vitro assays proved that CUR@CuTPyP/F68 could directly kill tumor cells by the released CUR and singlet oxygen (1O2) generated under laser irradiation (marked as '+'). Moreover, CUR@CuTPyP/F68 had superior tumor targeting and retention capabilities, which effectively inhibited tumor growth in vivo with only a single dose. Finally, the mechanism of CUR-mediated enhanced PDT had been firstly proposed: (1) CUR@CuTPyP/F68(+)-treated group exhibited more CD4+ and CD8+ T cells infiltration in tumor tissue; (2) CUR@CuTPyP/F68(+)-treated group exhibited high level of IFN-γ, IL-12 and TNF-α in blood. Overall, we believe the PDT-immunotherapy strategy has great potential for the treatment of breast cancer, and this work will provide a reference for the clinical application of essential oils in cancer immunotherapy.
    Keywords:  Curcumol; Essential oils; Immunotherapy; Metal-organic framework; Photodynamic therapy
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112456
  51. J Drug Target. 2022 Mar 14. 1-40
      Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammatory micro-environments in the joints. Indomethacin (IND), a conventional nonsteroidal anti-inflammatory drug (NSAID), has been used for therapy of RA. However, the poor solubility and serious side effects of oral administration of IND significantly limit its efficacy. In this study, we have synthesized biomimetic IND-loaded prussian blue (PB) nanoparticles (IND@PB@M@HA) with hyaluronic acid (HA) modification for increasing the solubility and targeting ability of IND to the inflamed joints. The application of hybrid cell membranes on the NPs endowed immune escape of IND@PB@M@HA NPs, which accordingly extended the circulation time in the blood. In vitro assay demonstrated that the combination of nanomedicine and photothermal therapy produced a powerful anti-inflammatory effect by reducing the levels of inflammatory factors and cell viability of activated macrophages and NPs possessed obvious pH-responsiveness. In vivo assay demonstrated that the nanomedicine for synergistic photothermal therapy exhibited desirable pharmacodynamics and pharmacokinetic properties at ultra-low drug dosage in a rat model of adjuvant-induced arthritis, which was confirmed by inflammatory suppression, bone erosion remission, and negligible adverse effects. In summary, the proposed nanomedicine has the potential role for targeted anti-inflammatory therapy of RA.
    Keywords:  Biomimetic membrane; Indomethacin; Photothermal therapy; Prussian blue nanoparticles; Rheumatoid arthritis; Targeted delivery
    DOI:  https://doi.org/10.1080/1061186X.2022.2053539
  52. Sci Rep. 2022 Mar 17. 12(1): 4574
      Artesunate was reported to have inhibition effect on tumors via amplified oxidative stress while the lack of intratumoral ferrous ions supply greatly hinders its efficacy. Herein, the AS/GOD@HAZnO NPs we proposed could be efficiently taken in by the affinity between hyaluronic acid and the CD44 receptors. DLS and TEM results manifested the nano-size (~ 160 nm) and circular shape of AS/GOD@HAZnO NPs. Due to the acid-responsive degradation, AS/GOD@HAZnO NPs realized responsive release (up to 80%) in acid environment while only 20% was released in neutral medium. The cellular and in vivo experiment showed that co-delivery of AS and GOD via HAZnO NPs could effectively induce the overproduction of ROS and cut the glucose supply of tumor cells, and thus result in efficient cell apoptosis and tumor inhibition.
    DOI:  https://doi.org/10.1038/s41598-022-08627-w
  53. Anal Bioanal Chem. 2022 Mar 16.
      The ability of silver nanoparticles (AgNPs) to be used as drug nanocarriers has helped rapidly to invent novel strategies to treat diseases, such as cancer. The nanoparticles may offer a valuable tool to novel pH-sensitive drug delivery systems in the present scenario because of their undergoing mechanisms associated with the regulated dissolution, aggregation, and generation of oxygen radicals as well. These processes could be monitored by electrochemical (bio)sensors that are less money and time-consuming compared to other analytical approaches, however, with comparable analytical performance. In this paper, synthesized and microscopically characterized gallic acid-coated AgNPs (GA-AgNPs) are investigated using spectral and electrochemical methods. To investigate the Ag+ release, a 21-day ageing experiment is performed spectrophotometrically, finding that the peak maximum of GA-AgNPs spectra diminished by 24.5%. The highest Ag+ content was electrochemically determined in the supernatant solution after centrifugation (6.97 μmol·L-1), while no significant concentration of silver ions in solution after redispersion was observed (1.26 μmol·L-1). The interaction experiment indicates a stabilization of GA-AgNPs in the presence of long-chain dsDNA as well as a mutual electrostatic interaction with DNA sugar-phosphate backbone. This interaction mechanism is confirmed by FTIR analysis, showing a shift (1049 to 1061 cm-1 and 913 to 964 cm-1) specific to DNA phosphate bands. Finally, doxorubicin-loaded GA-AgNPs are monitored for the specific drug release in the physiological and more reactive weakly acidic microenvironment. Hereby, electrochemical (bio)sensing of GA-AgNPs undergoing mechanisms shows a huge potential to be used for monitoring of drug delivery systems at cancer therapy.
    Keywords:  Aggregation; DNA interaction; Drug delivery system; Electrochemical biosensor; Silver ion release; Silver nanoparticles
    DOI:  https://doi.org/10.1007/s00216-022-03955-2
  54. Int J Biol Sci. 2022 ;18(4): 1451-1475
      Flavonoids are a group of polyphenolic compounds which are ubiquitously found in plants and are consumed as part of the human diet in substantial amounts. The verification of flavonoids' cancer chemopreventive benefits has led to a significant interest in this field. Gut microbiota includes a diverse community of microorganisms and has a close relationship with cancer development. Increasing evidence has indicated that flavonoids exert anticarcinogenic effects by reshaping gut microbiota. Gut microbiota can convert flavonoids into bioactive metabolites that possess anticancer activity. Here, we present a brief introduction to gut microbiota and provide an overview of the interplay between gut microbiota and cancer pathogenesis. We also highlight the crucial roles of flavonoids in preventing cancer based on their regulation of gut microbiota. This review would encourage research on the flavonoid-intestinal microbiota interactions and clinical trials to validate the chemotherapeutic potentials of targeting gut microbiota by dietary bioactive compounds.
    Keywords:  bioactive metabolites; cancer; chemopreventive benefits; flavonoids; gut microbiota
    DOI:  https://doi.org/10.7150/ijbs.68170
  55. Talanta. 2022 Mar 09. pii: S0039-9140(22)00167-9. [Epub ahead of print]243 123371
      Metallodrug delivery using magnetic nanomaterials is emerging as a tool for the treatment of cancer because of its potential of enhanced and controlled delivery to a specific site within the body, reduced side effects, and protection of drugs from the extracellular environment. In this brief review, we discuss recent progress in the development of iron oxide nanoparticles loaded with platinum anticancer drugs due to applying modern analytical techniques. Such techniques may vary depending on what step of manufacture and assessment of magnetic nanocarriers is in question, i.e., drug loading, payload stability, magnetic properties, drug release or the efficiency against different cancer cell lines. While focusing on a wider implementation of advanced analytical methodologies, we also critically contemplate how they help create more potent magnetic nanoformulations, resolve the current challenges with the use of magnetic nanomaterials in smart metallodrug delivery and thus accelerate their translation to human treatments.
    Keywords:  Anticancer metal-based drugs; Delivery; Drug carriers; ICP-MS; Magnetic nanoparticles
    DOI:  https://doi.org/10.1016/j.talanta.2022.123371
  56. J Control Release. 2022 Mar 14. pii: S0168-3659(22)00145-6. [Epub ahead of print]
      The effective treatment of glioma through conventional chemotherapy is proved to be a great challenge in clinics. The main reason is due to the existence of two physiological and pathological barriers respectively including the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) that prevent most of the chemotherapeutics from efficient delivery to the brain tumors. To address this challenge, an ideal drug delivery system would efficiently traverse the BBB and BBTB and deliver the therapeutics into the glioma cells with high selectivity. Herein, a targeted delivery system was developed based on nanostructured lipid carriers (NLCs) modified with two proteolytically stable D-peptides, D8 and RI-VAP (Dual NLCs). D8 possesses high affinity towards nicotine acetylcholine receptors (nAChRs), overexpressed on brain capillary endothelial cells (BCECs), and can penetrate through BBB with high efficiency. RI-VAP is a specific ligand of cell surface GRP78 (csGRP78), a specific angiogenesis and cancer cell-surface marker, capable of circumventing the BBTB with superior glioma-homing property. Dual NLCs could internalize into BCECs, tumor neovascular endothelial cells, and glioma cells with high specificity and could penetrate through in vitro BBB and BBTB models with excellent efficiency compared to non-targeted or mono-targeted NLCs. In vivo whole-animal imaging and ex vivo imaging further confirmed the superior targeting capability of Dual NLCs towards intracranial glioma. When loaded with Bortezomib (BTZ), Dual NLCs attained the highest therapeutic efficiency by means of in vitro cytotoxicity and apoptosis and prolonged survival rate and anti-glioma behavior in intracranial glioma bearing mice. Collectively, the designed targeting platform in this study could overcome multiple barriers and effectively deliver BTZ to glioma cells, which represent its potential for advanced brain cancer treatment with promising therapeutic outcomes.
    Keywords:  BBB; BBTB; D8; Glioma; NLCs; RI-VAP; Targeted drug delivery
    DOI:  https://doi.org/10.1016/j.jconrel.2022.03.019
  57. J Physiol. 2022 Mar;600(6): 1295-1297
      
    Keywords:  diet; exercise; fasting; metabolism; nutrition
    DOI:  https://doi.org/10.1113/JP282727
  58. Heliyon. 2022 Mar;8(3): e09030
      Intranasal drug transport through the olfactory route to the brain is an effective drug route for increased absorption and bioavailability of the drug. The objective of this study was to increase the penetration of valproic acid as an anticonvulsant into a delivery system comprising liposomes. Valproic acid liposomes were prepared by a thin-layer hydration technique using soybean phosphatidylcholine and cholesterol as the main ingredients. The formulations were evaluated for diameter size, entrapment efficiency (EE), zeta potential, polydispersity index, and morphology. ex vivo permeation using sheep nasal mucosa and in vivo efficacy were assessed by performing a pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison with pure drug. The mean size particle of optimized liposomes ranged from 90 to 210 nm with a low polydispersity index (<0.5). The EE of optimized liposomes was between 60% and 85%, increasing the concentration of phosphatidylcholine added to the formula. Transmission electron microscopy observations (40,000×) showed that valproic acid liposomes have a spherical molecular shape and a particle size of below 250 nm. The ex vivo and in vivo results showed that liposomal formulations provided enhanced brain exposure. Among the formulations studied, Formula 4 (F4) showed greater uptake of valproic acid into the brain than plasma. The high brain targeting efficiency index for F4 indicated the preferential transport of the drug to the brain. The study demonstrated the successful formulation of surface-modified valproic acid liposomes for nasal delivery with brain targeting potential.
    Keywords:  Brain; Epilepsy; Intranasal; Liposome; Penetration; Valproic acid
    DOI:  https://doi.org/10.1016/j.heliyon.2022.e09030
  59. MedComm (2020). 2022 Mar;3(1): e118
      Graphene-based materials have shown immense pertinence for sensing/imaging, gene/drug delivery, cancer therapy/diagnosis, and tissue engineering/regenerative medicine. Indeed, the large surface area, ease of functionalization, high drug loading capacity, and reactive oxygen species induction potentials have rendered graphene- (G-) and graphene oxide (GO)-based (nano)structures promising candidates for cancer therapy applications. Various techniques namely liquid-phase exfoliation, Hummer's method, chemical vapor deposition, chemically reduced GO, mechanical cleavage of graphite, arc discharge of graphite, and thermal fusion have been deployed for the production of G-based materials. Additionally, important criteria such as biocompatibility, bio-toxicity, dispersibility, immunological compatibility, and inflammatory reactions of G-based structures need to be systematically assessed for additional clinical and biomedical appliances. Furthermore, surface properties (e.g., lateral dimension, charge, corona influence, surface structure, and oxygen content), concentration, detection strategies, and cell types are vital for anticancer activities of these structures. Notably, the efficient accumulation of anticancer drugs in tumor targets/tissues, controlled cellular uptake properties, tumor-targeted drug release behavior, and selective toxicity toward the cells are crucial criteria that need to be met for developing future anticancer G-based nanosystems. Herein, important challenges and future perspectives of cancer therapy using G- and GO-based nanosystems have been highlighted, and the recent advancements are deliberated.
    Keywords:  cancer nanotherapy; graphene; graphene oxide; graphene‐based nanomaterials
    DOI:  https://doi.org/10.1002/mco2.118
  60. AAPS PharmSciTech. 2022 Mar 16. 23(4): 90
      Due to the high surface area, adjustable surface and pore structures, and excellent biocompatibility, nano- and micro-sized silica have certainly attracted the attention of many researchers in the medical fields. This review focuses on the multifunctional roles of silica in different pharmaceutical formulations including solid preparations, liquid drugs, and advanced drug delivery systems. For traditional solid preparations, it can improve compactibility and flowability, promote disintegration, adjust hygroscopicity, and prevent excessive adhesion. As for liquid drugs and preparations, like volatile oil, ethers, vitamins, and self-emulsifying drug delivery systems, silica with adjustable pore structures is a good adsorbent for solidification. Also, silica with various particle sizes, surface characteristics, pore structure, and surface modification controlled by different synthesis methods has gained wide attention owing to its unparalleled advantages for drug delivery and disease diagnosis. We also collate the latest pharmaceutical applications of silica sorted out by formulations. Finally, we point out the thorny issues for application and survey future trends pertaining to silica in an effort to provide a comprehensive overview of its future development in the medical fields. Graphical Abstract.
    Keywords:  drug delivery; micro-silica; modification; multi-function; nano-silica
    DOI:  https://doi.org/10.1208/s12249-022-02237-5
  61. Drug Deliv. 2022 Dec;29(1): 889-905
      As there is currently no effective therapy for patients with prostate cancer (PCa) bone metastasis, it was stringent to explore the relevant treatment strategies. Actually, the interaction between cancer cells and bone microenvironment plays important role in prostate cancer bone metastasis, especially the Sonic hedgehog protein (SHH) signaling in the bone microenvironment. The SHH promotes osteoblast maturation and osteoblast then secretes RANKL to induce osteoclastogenesis. Herein, this study develops bone-targeting calcium phosphate lipid hybrid nanoparticles (NPs) loaded with docetaxel (DTXL) and SHH siRNA for PCa bone metastasis treatment. For bone targeting purposes, the nanoplatform was modified with alendronate (ALN). (DTXL + siRNA)@NPs-ALN NPs effectively change the bone microenvironment by inhibiting the SHH paracrine and autocrine signaling, enhancing the anti-tumor effects of DTXL. Besides showing good in vitro cellular uptake, the NPs-ALN also inhibited tumor growth both in vitro and in vivo by inducing apoptosis, cell cycle arrest, and autophagy. This DDS comprised of (DTXL + siRNA)-loaded NPs provides an excellent strategy to treat PCa bone metastasis.
    Keywords:  Prostate cancer; bone metastasis; bone microenvironment; calcium phosphate nanoparticle; sonic hedgehog (SHH) protein
    DOI:  https://doi.org/10.1080/10717544.2022.2050845
  62. Nanomedicine (Lond). 2022 Mar 16.
      Aim: Synthesis of Fe3O4-Ag composite nanoparticles (NPs) by a new in situ reduction of Ag NPs on the surface of Fe3O4 NPs using gallic acid as a reducing agent. Materials & methods: The influence of process parameters on NP morphology and functionalization was evaluated by means of field-emission scanning/scanning transmission electron microscopy and Fourier-transform IR spectroscopy. Results & conclusion: The synthesis conditions affected the morphology of the obtained NPs, evidence of the formation of polydispersed aggregates, nanoflower-like or nanodumbbell nanocomposites. In particular, well-defined nanodumbbells were obtained in aqueous media, with an NP/gallic acid ratio of 10:1, while the presence of a silica shell did not improve the morphology of Ag NPs nucleated on the Fe3O4 core.
    Keywords:  gallic acid; in situ reduction; magnetic nanoparticle; silver nanoparticle
    DOI:  https://doi.org/10.2217/nnm-2021-0479
  63. Semin Cancer Biol. 2022 Mar 09. pii: S1044-579X(22)00064-5. [Epub ahead of print]
      Tumor heterogeneity is a hallmark of cancer and one of the primary causes of resistance to therapies. Triple-negative breast cancer (TNBC), which accounts for 15-20% of all breast cancers and is the most aggressive subtype, is very diverse, connected to metastatic potential and response to therapy. It is a very diverse disease at the molecular, pathologic, and clinical levels. TNBC is substantially more likely to recur and has a worse overall survival rate following diagnosis than other breast cancer subtypes. Chemokines, low molecular weight proteins that stimulate chemotaxis, have been shown to control the cues responsible for TNBC heterogeneity. In this review, we have focused on tumor heterogeneity and the role of chemokines in modulating tumor heterogeneity, since this is the most critical issue in treating TNBC. Additionally, we examined numerous cues mediated by chemokine networks that contribute to the heterogeneity of TNBC. Recent developments in our knowledge of the chemokine networks that regulate TNBC heterogeneity may pave the way for developing effective therapeutic modalities for effective treatment of TNBC.
    Keywords:  Breast cancer; Chemokines; EMT; Stemness; TNBC; Tumor heterogeneity
    DOI:  https://doi.org/10.1016/j.semcancer.2022.03.008
  64. Colloids Surf A Physicochem Eng Asp. 2022 May 20. pii: 128548. [Epub ahead of print]641
      Although the light-activated liposomes have been extensively studied for drug delivery applications, the fundamental mechanism of the drug release based on lipid compositions has not been fully understood. Especially, despite the extensive use of cholesterol in the lipid composition, the role of cholesterol in the light-activated drug release has not been studied. In this study, the influence of cholesterol on drug release from light-responsive drug-encapsulated liposomes after activated by near infrared (NIR) laser was investigated. We prepared methotrexate (MTX)-encapsulated DSPC liposomes consisting of 0 mol% (-Chol) or 35 mol% cholesterol (+Chol), with (+Au) or without gold nanorods (-Au) on the lipid bilayer to compare drug release, morphological changes, and nanostructures after laser irradiations. Transmission electron microscopy (TEM) and small angel neutron scattering (SANS) data revealed that only +Chol +Au liposomes showed partial aggregation of the liposomes after laser irradiation. Similar trends on the drug release and structural change were observed when the liposomes were heated to above chain-transition temperature. Overall, we have found that (1) inclusion of 35 mol% cholesterol enhanced the permeability of lipid bilayers above Tc; (2) the mechanism of laser-activated liposomal drug delivery is disrupting lipid bilayer membranes by the photothermal effect in the presence of plasmonic materials. By understanding the fundamentals of the technology, precise controlled drug release at a targeted site with great stability and repeatability is anticipated.
    Keywords:  Cholestero; Drug delivery; Light-activated liposomes; laser-activated drug release; neutron scattering
    DOI:  https://doi.org/10.1016/j.colsurfa.2022.128548
  65. J Cancer. 2022 ;13(4): 1130-1144
      Background: In the past few decades, natural products have become an increasingly important source of potential anti-cancer agents. The green walnut husk(GWH) extracts have been reported to inhibit multiple tumor cells and might be a promising chemopreventive agent in human neoplasia. However, it is not clear whether GWH extracts inhibit gastric cancer. Methods: Proliferation, invasion, and migration of gastric cancer cells were assessed by the CCK-8, wound-healing, and Transwell assay. The apoptotic rate was detected by flow cytometry(FCM). The expressions of Bcl-2, Bax, and Caspase-3 proteins were examined by Western blot. Moreover, the growth of gastric cancer cells was assessed using orthotopic xenograft models, and related proteins expressions were evaluated using immunohistochemistry. Finally, the Gene expression profile of gastric cancer treated with GWH extracts was evaluated by using High-throughput RNA sequencing(RNA-seq). Results: GWH extracts effectively inhibited gastric cancer cell growth in vitro and in vivo. In vivo, GWH extracts inhibited the survival of gastric cancer cells in a dose and time-dependent manner, inhibited the migration and invasion of gastric cancer cells, regulated the expressions of apoptosis-related proteins, and induced apoptosis of gastric cancer cells. In vitro, GWH extracts inhibited the growth of mouse xenografted tumors. A total of differentially expressed genes, of which 41 genes were up-regulated, and 610 genes were down-regulated, were identified by RNA-seq. GO, and KEGG analysis showed that these differentially expressed genes might be related to the mechanism of the anti-gastric cancer effect of GWH extracts. Conclusion: GWH extracts played an anti-gastric cancer effect by inducing apoptosis and inhibiting invasion. Secondly, the differential expression of many genes, multiple signal pathways, and metabolic pathways in gastric cancer play an essential role in the anti-gastric cancer effect of GWH extracts. The results suggested that GWH extracts are expected to be a low toxic drug for the treatment of gastric cancer in the future.
    Keywords:  Anticancer; Cell apoptosis; Gastric cancer; The green walnut husk
    DOI:  https://doi.org/10.7150/jca.57270
  66. Chin J Dent Res. 2022 Mar 16. 25(1): 11-20
      Extensive research has indicated that high glucose levels play an important role in cancer. A high glycaemic index, glycaemic load diet, high sugar intake, high blood glucose and diabetes mellitus all increase the risk of cancer. Various signals are involved in high glucose-induced tumorigenesis, cancer proliferation, apoptosis, invasion and multidrug resistance. Reactive oxygen species might be important targets in cancer progression that are induced by high glucose levels. Drugs such as metformin and resveratrol may inhibit high glucose-induced cancer. As the impact of high glucose levels on cancer progression and therapy is a novel finding, further research is required.
    Keywords:  cancer; high glucose; progression; therapy; tumorigenesis
    DOI:  https://doi.org/10.3290/j.cjdr.b2752695
  67. Pol Merkur Lekarski. 2022 Feb 22. 50(295): 62-64
      Diabetes as chronic civilization disease, very often occurs together with health disorders. One of the basic pharmaceuticals commonly used in her therapy is metformin. Many other positive effects, not related to diabetes, have been observed in tatients treated with metformin for a long time. These are: positive changes in diagnostiic parameters, protection against cancer development, less frequent occurrence of other pathologies and diseases, increased sensitivity to selected drugs (e.g. cytostatics), delayed aging processes of organism. In addition to the molecular changes resulting in a hypoglycemic effect, the most common modifications of gene expression have been described, indicated as the basis for the anti-aging, anti-atherosclerotic and anticancer effects of this drug and its effect on melanogenesis or the nervous system. The results presented in the study are very promising, but most of them relate to experiments carried out in cell cultures or animals. The possibility of obtaining similar effects in humans requires much more research.
    Keywords:  mechanism of action; metformin
  68. Egypt J Intern Med. 2022 ;34(1): 26
       Background: Herbs are commonly used to treat cardiovascular diseases in various traditional medicine. On the other hand, herb-drug interactions are most commonly encountered with conventional antiplatelet and anticoagulant drug prescriptions. This review presents a compilation of plants investigated for antiplatelet and anticoagulation recently and enumerates their possible lead compounds responsible for its action for paving further drug discovery and knowledge update.
    Main body of the abstract: Information about the herbs was withdrawn from the PubMed database of the previous 5 years. We also hand-searched the bibliography of relevant articles for the acquisition of additional information. About 72 herbal sources were identified with the effect of antiplatelet activity, antithrombotic activity, and anticoagulant activity. Bioactive compounds and various secondary metabolites responsible for it, such as alkaloids, saponins, flavonoids, coumarins, polyphenols, furan derivatives, iridoid glycosides, sesquiterpenes, aporphine compounds, were reported.
    Conclusion: Newer pharmacological moieties are needed to prevent or reduce the adverse effects of current anti-thrombotic agents and to improve the safety of patients and cost-effectiveness.
    Keywords:  Alkaloids; Anticoagulant; Antiplatelet; Antithrombotic; Coumarins; Flavonoids; Herbal medicine; Phytochemicals; Saponins; Secondary metabolites
    DOI:  https://doi.org/10.1186/s43162-021-00090-9
  69. J Colloid Interface Sci. 2022 Mar 10. pii: S0021-9797(22)00423-4. [Epub ahead of print]617 542-556
      Diabetic wound treatment remains a major challenge due to the difficulties of eliminating bacterial biofilm and relieving wound hypoxia. To address these issues simultaneously, a multifunctional Dex-SA-AEMA/MnO2/PDA (DSAMP) hydrogel platform was developed with excellent biocompatibility and porous structure. The hydrogel could absorb the exudate, maintain humidity and permeate oxygen, which was prepared by encapsulating polydopamine (PDA) and manganese dioxide (MnO2) into Dex-SA-AEMA (DSA) hydrogel by UV irradiation. With the addition of PDA, the DSAMP hydrogel was proved to eliminate the biofilm after NIR photodynamic therapy (PTT, 808 nm) irradiation at 54 °C. Furthermore, in order to mitigate hypoxia wound microenvironment, MnO2 nanoparticles were added to convert the endogenous hydrogen peroxide (H2O2) into oxygen (O2, 16 mg L-1). The diabetic wound in vivo treated by DSAMP hydrogel was completely healed on 14 days. It was revealed that the DSAMP hydrogel possessed a great potential as dressing for diabetic chronic wound healing.
    Keywords:  Antibacterial properties; Biofilm removal; Diabetic wound healing; O(2) generation; Photothermal effect
    DOI:  https://doi.org/10.1016/j.jcis.2022.03.040
  70. J Nutr Sci. 2022 ;11 e13
      Since the discovery of vitamin D, it has been accepted that its physiological supply is either from food or by endogenous synthesis in skin exposed to solar UV light. Yet vitamin D is a component of very few foods and its supply as a natural nutrient is unable to maintain good vitamin D status for human populations. One aspect of vitamin D physiology that has been ignored is that the mechanisms for its transport and processing from these two sources are quite different. Excess intake of vitamin D causes hypercalcaemic toxicity. However, experiments with different animal species have shown that long-term supply of oral vitamin D in apparently non-toxic amounts causes atherosclerosis in large arteries. A mechanism for this toxicity is proposed. Alternative strategies for addressing widespread vitamin D deficiency by food fortification should be considered in light of the angiotoxicity caused by oral vitamin D in animal experiments.
    Keywords:  25(OH)D, 25-hydroxy vitamin D; 25-hydroxyvitamin D production; 25-hydroxyvitamin D toxicity; 7-DHC, 7-dehydrocholesterol; Angiotoxicity; DBP, vitamin D-specific-binding protein; Vitamin D transport
    DOI:  https://doi.org/10.1017/jns.2022.11
  71. Front Cell Dev Biol. 2022 ;10 844050
      There has been a rapid development of biomimetic platforms using cell membranes as nanocarriers to camouflage nanoparticles for enhancing bio-interfacial capabilities. Various sources of cell membranes have been explored for natural functions such as circulation and targeting effect. Biomedical applications of cell membranes-based delivery systems are expanding from cancer to multiple diseases. However, the natural properties of cell membranes are still far from achieving desired functions and effects as a nanocarrier platform for various diseases. To obtain multi-functionality and multitasking in complex biological systems, various functionalized modifications of cell membranes are being developed based on physical, chemical, and biological methods. Notably, many research opportunities have been initiated at the interface of multi-technologies and cell membranes, opening a promising frontier in therapeutic applications. Herein, the current exploration of natural cell membrane functionality, the design principles for engineered cell membrane-based delivery systems, and the disease applications are reviewed, with a special focus on the emerging strategies in engineering approaches.
    Keywords:  cell membrane camouflaged nanoparticles; drug delivery; membrane engineering; multi-functionality; targeting effect
    DOI:  https://doi.org/10.3389/fcell.2022.844050
  72. Front Oncol. 2022 ;12 819563
      Cancer is a multifaceted global health issue and one of the leading causes of death worldwide. In recent years, medical science has achieved great advances in the diagnosis and treatment of cancer. Despite the numerous advantages of conventional cancer therapies, there are major drawbacks including severe side effects, toxicities, and drug resistance. Therefore, the urgency of developing new drugs with low cytotoxicity and treatment resistance is increasing. Antimicrobial peptides (AMPs) have attracted attention as a novel therapeutic strategy for the treatment of various cancers, targeting tumor cells with less toxicity to normal tissues. In this review, we present the structure, biological function, and underlying mechanisms of AMPs. The recent experimental studies and clinical trials on anticancer peptides in different cancer types as well as the challenges of their clinical application have also been discussed.
    Keywords:  angiogenesis; anticancer peptides (ACPs); antimicrobial peptides (AMPs); apoptosis; cancer; exosome; mechanism
    DOI:  https://doi.org/10.3389/fonc.2022.819563
  73. Beilstein J Nanotechnol. 2022 ;13 255-264
      Melanoma is one of the deadliest forms of cancer, for which therapeutic regimens are usually limited by the development of resistance. Here, we fabricated Fe3O4 nanoparticle clusters (NPCs), which have drawn widespread attention, and investigated their role in the treatment of melanoma by photothermal therapy (PTT). Scanning electron microscopy imaging shows that our synthesized NPCs are spherical with an average diameter of 329.2 nm. They are highly absorptive at the near-infrared wavelength of 808 nm and efficient at locally converting light into heat. In vitro experiments using light-field microscopy and cell viability assay showed that Fe3O4 NPCs, in conjunction with near-infrared irradiation, effectively ablated A375 melanoma cells by inducing overt apoptosis. Consistently, in vivo studies using BALB/c mice found that intratumoral administration of Fe3O4 NPCs and concomitant in situ exposure to near-infrared light significantly inhibited the growth of implanted tumor xenografts. Finally, we revealed, by experimental approaches including semi-quantitative PCR, western blot and immunohistochemistry, the heat shock protein HSP70 to be upregulated in response to PTT, suggesting this chaperone protein could be a plausible underlying mechanism for the observed therapeutic outcome. Altogether, our results highlight the promise of Fe3O4 NPCs as a new PTT option to treat melanoma.
    Keywords:  Fe3O4 nanoparticle clusters; heat shock protein 70; melanoma; near infrared; photothermal therapy
    DOI:  https://doi.org/10.3762/bjnano.13.20
  74. Front Pharmacol. 2022 ;13 827520
      Paclitaxel (PTX) has been the first-line treatment for lung cancer; however, its clinical use is limited due to multidrug resistance (MDR) and adverse effects. Thus, there is an urgent need to explore agents that can enhance the anticancer efficacy of PTX by reducing drug resistance and adverse reactions. Jiegeng decoction (JG) was used as the meridian guide drug and adjuvant drug in treatment of lung cancer. However, the mechanism of adjuvant effect was unclear. The aim of this study was to determine whether JG could potentiate the anticancer effect of PTX. Tissue distribution of PTX was detected using HPLC-MS/MS. The anti-lung cancer effect of the combination of PTX and JG in Lewis lung cancer C57BL/6J mice was evaluated based on the body weight and tumor-inhibition rate. PTX concentration in tumors was determined using HPLC-MS and in vivo imaging. Biochemical indices were detected using biochemical analyzer and ELISA. The anticancer mechanism of the PTX-JG combination in A549/PTX cells was elucidated based on cell proliferation, annexin V-FITC apoptosis assay, and western blotting. Tissue distribution analysis showed that the distribution of PTX increased in the lungs, liver, and heart upon administering the combination of PTX and JG. JG remarkably enhanced the anticancer effect of PTX by increasing the red blood cell and platelet counts; increasing hemoglobin, interleukin (IL)-2, and tumor necrosis factor-α levels; increasing CD4+T cells and the CD4+/CD8+ ratio; and decreasing IL-10 levels. JG administration led to the increased distribution of PTX at the tumor lesion sites and also potentiated the anticancer effect of PTX by inhibiting tumor cell proliferation and promoting apoptosis. Moreover, JG reversed PTX resistance by inhibiting the expression of lung resistance-related proteins, multiresistance protein 1, P-glycoprotein, and breast cancer-resistant protein. Furthermore, the combination of JG and PTX decreased alanine aminotransferase and aspartate aminotransferase levels and did not affect creatine kinase-MB levels. Therefore, our discovery suggests that JG increased the anticancer effect of PTX by downregulating the MDR-related protein and demonstrated a synergistic enhancement of immunity. Thus, the combination of PTX with JG shows potential in the management of lung cancer owing to its synergistic and detoxifying effects.
    Keywords:  MDR; anti-cancer; gancao; jiegeng; meridian guide effect; paclitaxel
    DOI:  https://doi.org/10.3389/fphar.2022.827520
  75. J Genet Eng Biotechnol. 2022 Mar 16. 20(1): 48
       BACKGROUND: Omega-9 fatty acids represent one of the main mono-unsaturated fatty acids (MUFA) found in plant and animal sources. They are synthesized endogenously in humans, though not fully compensating all body requirements. Consequently, they are considered as partially essential fatty acids. MUFA represent a healthier alternative to saturated animal fats and have several health benefits, including anti-inflammatory and anti-cancer characters. This review capitalizes on the major omega-9 pharmacological activities in context of inflammation management for its different natural forms in different dietary sources. The observed anti-inflammatory effects reported for oleic acid (OA), mead acid, and erucic acid were directed to attenuate inflammation in several physiological and pathological conditions such as wound healing and eye inflammation by altering the production of inflammatory mediators, modulating neutrophils infiltration, and altering VEGF effector pathway. OA action mechanisms as anti-tumor agent in different cancer types are compiled for the first time based on its anti- and pro-carcinogenic actions.
    CONCLUSION: We conclude that several pathways are likely to explain the anti-proliferative activity of OA including suppression of migration and proliferation of breast cancer cells, as well stimulation of tumor suppressor genes. Such action mechanisms warrant for further supportive clinical and epidemiological studies to confirm the beneficial outcomes of omega-9 consumption especially over long-term intervention.
    Keywords:  Inflammation; anti-cancer; oleic acid; MUFA; Omega-9; PUFA
    DOI:  https://doi.org/10.1186/s43141-022-00329-0
  76. Trends Cell Biol. 2022 Mar 14. pii: S0962-8924(22)00036-8. [Epub ahead of print]
      Gene transcription and cell metabolism are two fundamental biological processes that mutually regulate each other. Upregulated or altered expression of glucose metabolic genes in glycolysis and gluconeogenesis is a major driving force of enhanced aerobic glycolysis in tumor cells. Importantly, glycolytic and gluconeogenic enzymes in tumor cells acquire moonlighting functions and directly regulate gene expression by modulating chromatin or transcriptional complexes. The mutual regulation between cellular metabolism and gene expression in a feedback mechanism constitutes a unique feature of tumor cells and provides specific molecular and functional targets for cancer treatment.
    Keywords:  cancer; gene expression; gluconeogenesis; glycolysis; metabolism
    DOI:  https://doi.org/10.1016/j.tcb.2022.02.003
  77. Ann Transl Med. 2022 Feb;10(4): 234
       Background and Objective: The ginsenoside compound K [20-o-beta-dglucopyranosyl-20 (S)-protopanaxadiol; CK] is the main deglycosylated metabolite of ginsenoside. As a rare ginsenoside converted from the active substance of ginseng by intestinal bacteria, CK has higher biological activity than other ginsenosides. It has demonstrated diverse and intriguing biological activities, including anti-carcinogenic, anti-diabetic, anti-inflammation, anti-allergy, anti-angiogenesis, anti-aging, neuroprotective, and hepatoprotective effects. The purpose of this review was to elucidate the rich pharmacological activities and related mechanisms of ginsenoside CK in vivo and in vitro, as well as the potential therapeutic value of CK as a drug in a variety of systemically related diseases.
    Methods: The PubMed database was searched for articles published in English from February 2008 to December 2021 using related keywords such as "Ginsenoside compound K", "compound K", and "CK". About 140 research papers and reports written in English were identified. These papers mainly concentrated on the pharmacological activities of CK in cancer prevention, immune regulation, diabetic improvement, central nervous system (CNS) protection, cardiovascular protection, skin improvement, and hepatoprotection.
    Key Content and Findings: This paper describes the synthesis, pharmacokinetics, and adverse reactions of CK, as well as great detailed summarized of the relevant pharmacological activities. Such diverse intriguing biological properties of CK have been found.
    Conclusions: On account of CK's numerous pharmacological activities and anti-carcinogenic, anti-inflammation, antiallergic, anti-diabetic, anti-angiogenesis, anti-aging, neuroprotective, and hepatoprotective effects, strong evidence is available for CK as a preventive or therapeutic agent for various diseases. However, further studies are needed to evaluate the safety and effectiveness of CK as a drug and its application in the medical field.
    Keywords:  Ginsenoside compound K; cancer; diabetes; pharmacology
    DOI:  https://doi.org/10.21037/atm-22-501
  78. Int J Pharm. 2022 Mar 15. pii: S0378-5173(22)00188-0. [Epub ahead of print] 121633
       AIM: Evaluation of different polyhydroxy surfaces in SEDDS to overcome the limitations associated with conventional polyethylene glycol (PEG)-based SEDDS surfaces for intracellular drug delivery.
    METHODS: Anionic, cationic and non-ionic polyglycerol- (PG-) and alkylpolyglucoside- (APG-) surfactant based SEDDS were developed and compared to conventional PEG-SEDDS. Particular emphasis was placed on the impact of SEDDS surface decoration on size and zeta potential, drug loading and protective effect, mucus diffusion, SEDDS-cell interaction and intracellular delivery of the model drug curcumin.
    RESULTS: After self-emulsification, SEDDS droplets sizes were within the range of 35-190 nm. SEDDS formulated with high amounts of long PEG-chain surfactants (> 10 monomers) a charge-shielding effect was observed. Replacing PEG-surfactants with PG- and an APG-surfactant did not detrimentally affect SEDDS self-emulsification, payloads or the protection of incorporated curcumin towards oxidation. PG- and APG-SEDDS bearing multiple hydroxy functions on the surface demonstrated mucus permeation comparable to PEG-SEDDS. Steric hinderance and charge-shielding of PEG-SEDDS surface substantially reduced cellular uptake up to 50-fold and impeded endosomal escape, yielding in a 20-fold higher association of PEG-SEDDS with lysosomes. In contrast, polyhydroxy-surfaces on SEDDS promoted pronounced cellular internalisation and no lysosomal co-localisation was observed. This improved uptake resulted in an over 3-fold higher inhibition of tumor cell proliferation after cytosolic curcumin delivery.
    CONCLUSION: The replacement of PEG-surfactants by surfactants with polyhydroxy head groups in SEDDS is a promising approach to overcome the limitations for intracellular drug delivery associated with conventional PEGylated SEDDS surfaces.
    Keywords:  PEG-free; intracellular drug delivery; polyglycerol; polyhydroxy; saccharide; self-emulsifying drug delivery system (SEDDS); surface modification
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.121633
  79. J Nanobiotechnology. 2022 Mar 15. 20(1): 132
      Extracellular vesicles (EVs) are a group of secretory vesicles with cell-derived membrane and contents. Due to the cargo delivery capability, EVs can be designed as drug delivery platforms for cancer therapy. Biocompatibility and immune compatibility endow EVs with unique advantages compared with other nanocarriers. With the development of this field, multiple ingenious modification methods have been developed to obtain engineered EVs with desired performance. Application of engineered EVs in cancer therapy has gradually shifted from monotherapy to combinational therapy to fight against heterogeneous cancer cells and complex tumor microenvironment. In addition, the strong plasticity and load capacity of engineered EV make it potential to achieve various combinations of cancer treatment methods. In this review, we summarize the existing schemes of cancer combination therapy realized by engineered EVs, highlight the mechanisms and representative examples of these schemes and provide guidance for the future application of engineered EVs to design more effective cancer combination treatment plans.
    Keywords:  Cancer therapy; Combinational therapy; Engineered EVs; Extracellular vesicles (EVs)
    DOI:  https://doi.org/10.1186/s12951-022-01330-y
  80. Bioconjug Chem. 2022 Mar 14.
      Active targeting strategies aimed at improving drug homing while reducing systemic toxicity are widely being pursued in the growing field of nanomedicine. While they can be effective, these approaches often require the identification of cell-specific targets and in-depth knowledge of receptor binding interactions. More recently, there has been significant interest in biomimetic nanoformulations capable of replicating the properties of naturally occurring systems. In particular, the advent of cell membrane coating nanotechnology has enabled researchers to leverage the inherent tropisms displayed by living cells, bypassing many of the challenges associated with traditional bottom-up nanoengineering. In this work, we report on a biomimetic organotropic nanodelivery system for localizing therapeutic payloads to the lungs. Metastatic breast cancer exosomes, which are lung tropic due to their unique surface marker expression profile, are used to coat nanoparticle cores loaded with the anti-inflammatory drug dexamethasone. In vivo, these nanoparticles demonstrate enhanced accumulation in lung tissue and significantly reduce proinflammatory cytokine burden in a lung inflammation model. Overall, this work highlights the potential of using biomimetic organ-level delivery strategies for the management of certain disease conditions.
    DOI:  https://doi.org/10.1021/acs.bioconjchem.1c00599
  81. Rev Diabet Stud. 2022 Mar 09. 18(1): 10-19
      BACKGROUND: Early time-restricted feeding (eTRF) is a new dietary strategy, involving extended fasting (≥14h) from mid- afternoon onwards with or without calorie restriction. Most of the published studies indicate controversial effects on several glycemic markers. AIM : To evaluate the effect of non-calorie restricted eTRF on the glycemic profile of adults. METHOD: this systematic review was designed according to PRISMA guidelines. Pubmed/ Medline, the Cochrane library and EBSCO electronic databases were systematically searched for eligible clinical trials. Studies with eTRF or with daily fasting regimens that presented all the characteristics of eTRF were selected and compared with regular diet schedules or delayed time-restricted feeding. Blood glucose and insulin markers were extracted from each study as the main outcome measures. RESULTS: Five articles including 67 adult subjects in total were selected. The period of intervention varied between 3 days to 5 weeks. Three of the included studies were diet- controlled for weight maintenance, whereas the other two studies allowed for free living. Quality assessment identified two studies of low and three studies of high risk of bias. two studies showed clear positive effects of eTRF on both glucose and insulin markers, including fasting glucose levels, muscle glucose intake, glucose iAUC responses insulin levels, and insulin resistance (p<0.05). Two other studies showed beneficial effects on glucose markers only (fasting glucose, 24h mean glucose levels, and iAUC responses, p<0.05) and the fifth study showed positive effects on insulin markers only (insulin resistance, p<0.05). CONCLUSIONS: eTRF seems to have positive effects on the glycemic profile mainly in healthy individuals with normal BMI. However, other factors should also be taken into account to address overweight, obese, and prediabetic individuals. Further research is required to clarify better the effectiveness of eTRF among individuals with different characteristics.
    DOI:  https://doi.org/10.1900/RDS.2022.18.10
  82. Phytomedicine. 2022 Mar 03. pii: S0944-7113(22)00091-5. [Epub ahead of print]99 154013
       INTRODUCTION: The genus Callistemon belongs to a group of medically significant plants which have found tremendous use in traditional medicine across the globe. They are reported for anti-cancer, neuroprotective, anti-inflammatory, antioxidant, anti-microbial, and many other significant medicinal attributes. However, the current use of this genus is limited mainly to ornamental and recreational purposes. Recent studies have reported several novel compounds like phloroglucinol derivatives, terpenes, phenolics, etc., from Callistemon spp., which have great medical significance. Further, there is a surge of recent studies reporting novel pharmacological properties of Callistemon. The number of review studies discussing the underlying molecular mechanism behind the pharmacological action of Callistemon is quite limited.
    METHODS: The literature search for studies published from 1991 to 2021 using Google scholar and PubMed were selected. The review documented relevant literature focused on Callistemon spp exhibiting significant pharmacological effects.
    RESULTS: This review deals with the pharmacological properties of Callistemon and the underlying molecular mechanism responsible for protective effect in several pathophysiological conditions. This study updated the current information regarding the medicinal importance of Callistemon spp. for research and the public community.
    DISCUSSION AND CONCLUSIONS: The preliminary studies, interrogating pharmacological properties of Callistemon spp., hold great promise and demand further research to decipher the mode of action. More and more research are needed in this direction to explore the full potential of the genus Callistemon as a medicinal herb.
    Keywords:  Callistemon; Molecular mechanism; Pharmacological activity; Phytoconstituents
    DOI:  https://doi.org/10.1016/j.phymed.2022.154013
  83. Int J Pharm X. 2022 Dec;4 100114
      Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a long-term condition resulting from self-sustained intestinal inflammation. Curcumin (Cur), a powerful, naturally occurring antioxidant and anti-inflammatory polyphenol, has been investigated as a therapeutic for IBD, but its poor stability and low bioavailability limits its efficacy. We investigated the use of crosslinked starch nanocarrier (NPL) on the intracellular delivery and the anti-inflammatory efficiency of curcumin. Caco-2 epithelial cells were stimulated with TNFα for 24 h and the anti-inflammatory effects of NPL/Cur formulations were evaluated at the early stages of inflammation (4 h) or later, when fully established (24 h). NPL allowed the intracellular delivery of curcumin, which was enhanced in inflammatory cells, due to a modification of the endocytosis pathways. NPL/Cur decreased the secretion of pro-inflammatory cytokines IL-1β, IL-6 and IL-8 while increasing the anti-inflammatory cytokine IL-10. Finally, the inflammation-related opening of the tight junctions better allowed NPL/Cur to cross the epithelium by paracellular transport. This was confirmed by ex vivo analysis where NPL/Cur, administered to colonic explants from chemically-induced acute colitis mouse model, delivered curcumin deeper in the epithelium. To conclude, NPL/Cur formulation emphasizes the anti-inflammatory effects of curcumin and could constitute a therapeutic alternative in the management of IBD.
    Keywords:  Bowel disease; Curcumin; Delivery system; Inflammation; Mucosal delivery; Nanoparticles
    DOI:  https://doi.org/10.1016/j.ijpx.2022.100114