Astaxanthin-loaded alginate-chitosan gel beads activate Nrf2 and pro-apoptotic signalling pathways against oxidative stress.

Oxidative stress (OS) plays a crucial role in disease development. Astaxanthin (ATX), a valuable natural compound, may reduce OS and serve as a treatment for diseases like neurodegenerative disorders and cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates antioxidant enzymes and OS management. We evaluated ATX's antioxidant activity via Alg-CS/ATX gel beads in vitro. ATX-encapsulated alginate-chitosan (Alg-CS/ATX) gel beads were synthesized and structurally/morphologically characterized by SEM, FT-IR, and XRD. Their biological effects were examined in human umbilical vein endothelial cells (HUVECs) treated with H2O2 through MTT assay, Annexin V/PI, cell cycle studies, and western blotting. Alg-CS effectively carried ATX, with high capacity and reduced pore size. Alg-CS/ATX displayed an 84% encapsulation efficiency, maintaining stability for 30 days. In vitro studies showed a 1.4-fold faster release at pH 5.4 than at neutral pH, improving ATX's therapeutic potential. HUVECs treated with Alg-CS/ATX showed enhanced viability via increased Nrf2 expression. Alg-CS gel beads exhibit significant potential as a biocompatible vehicle for delivering ATX to combat OS with considerable opportunity for clinical applications.

Fabrication of mesoporous silica nanoparticles for targeted delivery of sunitinib to ovarian cancer cells.

Introduction: Mesoporous silica nanoparticles (MSNPs) are considered innovative multifunctional structures for targeted drug delivery owing to their outstanding physicochemical characteristics. Methods: MSNPs were fabricated using the sol-gel method, and polyethylene glycol-600 (PEG600) was used for MSNPs modification. Subsequently, sunitinib (SUN) was loaded into the MSNPs, MSNP-PEG and MSNP-PEG/SUN were grafted with mucin 16 (MUC16) aptamers. The nanosystems (NSs) were characterized using FT-IR, TEM, SEM, DLS, XRD, BJH, and BET. Furthermore, the biological impacts of MSNPs were evaluated on the ovarian cancer cells by MTT assay and flow cytometry analysis. Results: The results revealed that the MSNPs have a spherical shape with an average dimension, pore size, and surface area of 56.10 nm, 2.488 nm, and 148.08 m2g-1, respectively. The cell viability results showed higher toxicity of targeted MSNPs in MUC16 overexpressing OVCAR-3 cells as compared to the SK-OV-3 cells; that was further confirmed by the cellular uptake results. The cell cycle analysis exhibited that the induction of sub-G1 phase arrest mostly occurred in MSNP-PEG/SUN-MUC16 treated OVCAR-3 cells and MSNP-PEG/SUN treated SK-OV-3 cells. DAPI staining showed apoptosis induction upon exposure to targeted MSNP in MUC16 positive OVCAR-3 cells. Conclusion: According to our results, the engineered NSs could be considered an effective multifunctional targeted drug delivery platform for the mucin 16 overexpressing cells.

Advanced nanoscale drug delivery systems for bone cancer therapy.

Bone tumors are relatively rare, which are complex cancers and primarily involve the long bones and pelvis. Bone cancer is mainly categorized into osteosarcoma (OS), chondrosarcoma, and Ewing sarcoma. Of these, OS is the most intimidating cancer of the bone tissue, which is mostly found in the log bones in young children and older adults. Conspicuously, the current chemotherapy modalities used for the treatment of OS often fail mainly due to (i) the non-specific detrimental effects on normal healthy cells/tissues, (ii) the possible emergence of drug resistance mechanisms by cancer cells, and (iii) difficulty in the efficient delivery of anticancer drugs to the target cells. To impose the maximal therapeutic impacts on cancerous cells, it is of paramount necessity to specifically deliver chemotherapeutic agents to the tumor site and target the diseased cells using advanced nanoscale multifunctional drug delivery systems (DDSs) developed using organic and inorganic nanoparticles (NPs). In this review, we provide deep insights into the development of various DDSs applied in targeting and eradicating OS. We elaborate on different DDSs developed using biomaterials, including chitosan, collagen, poly(lactic acid), poly(lactic-co-glycolic acid), polycaprolactone, poly(ethylene glycol), polyvinyl alcohol, polyethyleneimine, quantum dots, polypeptide, lipid NPs, and exosomes. We also discuss DDSs established using inorganic nanoscale materials such as magnetic NPs, gold, zinc, titanium NPs, ceramic materials, silica, silver NPs, and platinum NPs. We further highlight anticancer drugs' role in bone cancer therapy and the biocompatibility of nanocarriers for OS treatment.

Targeted Delivery of Sunitinib by MUC-1 Aptamer-Capped Magnetic Mesoporous Silica Nanoparticles.

Magnetic mesoporous silica nanoparticles (MMSNPs) are being widely investigated as multifunctional novel drug delivery systems (DDSs) and play an important role in targeted therapy. Here, magnetic cores were synthesized using the thermal decomposition method. Further, to improve the biocompatibility and pharmacokinetic behavior, mesoporous silica was synthesized using the sol-gel process to coat the magnetic cores. Subsequently, sunitinib (SUN) was loaded into the MMSNPs, and the particles were armed with amine-modified mucin 1 (MUC-1) aptamers. The MMSNPs were characterized using FT-IR, TEM, SEM, electrophoresis gel, DLS, and EDX. MTT assay, flow cytometry analysis, ROS assessment, and mitochondrial membrane potential analysis evaluated the nanoparticles' biological impacts. The physicochemical analysis revealed that the engineered MMSNPs have a smooth surface and spherical shape with an average size of 97.6 nm. The biological in vitro analysis confirmed the highest impacts of the targeted MMSNPs in MUC-1 overexpressing cells (OVCAR-3) compared to the MUC-1 negative MDA-MB-231 cells. In conclusion, the synthesized MMSNP-SUN-MUC-1 nanosystem serves as a unique multifunctional targeted delivery system to combat the MUC-1 overexpressing ovarian cancer cells.

Smart chitosan-folate hybrid magnetic nanoparticles for targeted delivery of doxorubicin to osteosarcoma cells.

Chitosan (CS)-based pH-sensitive nanocomposites were fabricated for the targeted delivery of doxorubicin (DOX) to osteosarcoma cells. To prepare the nanocomposite, CS was functionalized with succinic anhydride (SA) (CS-SA). CS-folic acid (FA) conjugates were produced by the conjugation of CS with FA via an amide bond. Next, Fe3O4 magnetic nanoparticles (MNPs) ferrofluid was fabricated, and nanocomposite was produced using MNPs and synthesized CS-SA/CS-FA and CS-SA via an inclusion formation between -COOH groups of CS-SA and hydroxyl groups of Fe3O4. Finally, DOX molecules were loaded onto the nanocomposites. The nanocomposites were characterized through FT-IR, DLS, XRD, VSM, TEM, and UV-Vis spectroscopy analyses. DOX release profile at various pHs indicated an enhanced release of DOX in acidic conditions. The cytotoxicity assay demonstrated that the nanocarriers alone were cytocompatible on cells examined. The MG-63 cells, which partly express the folate receptors (FRs), particularly FR-α, showed meaningfully higher cellular uptake of the DOX-loaded CS-FA/CS-SA@MNPs than the FR-negative lung cancer A549 cells. The DOX-loaded CS-FA/CS-SA-MNPs could induce significant cytotoxicity in the MG-63 cells but not in A549 cells. Based on these findings, the DOX-loaded CS-FA/ CS-SA-MNPs might be considered a smart pH-sensitive nanosystem for the targeted delivery of anticancer agents to osteosarcoma cancer cells.

Optogenetics: A new tool for cancer investigation and treatment.

Despite the progress made in the diagnosis and treatment of cancer, it has remained the second cause of death in industrial countries. Cancer is a complex multifaceted disease with unique genomic and proteomic hallmarks. Optogenetics is a biological approach, in which the light-sensitive protein modules in combination with effector proteins that trigger reversibly fundamental cell functions without producing a long-term effect. The technology was first used to address some key issues in neurology. Later on, it was also used for other diseases such as cancer. In the case of cancer, there exist several signaling pathways with key proteins that are involved in the initiation and/or progression of cancer. Such aberrantly expressed proteins and the related signaling pathways need to be carefully investigated in terms of cancer diagnosis and treatment, which can be managed with optogenetic tools. Notably, optogenetics systems offer some advantages compared to the traditional methods, including spatial-temporal control of protein or gene expression, cost-effective and fewer off-target side effects, and reversibility potential. Such noticeable features make this technology a unique drug-free approach for diagnosis and treatment of cancer. It can be used to control tumor cells, which is a favorable technique to investigate the heterogeneous and complex features of cancerous cells. Remarkably, optogenetics approaches can provide us with outstanding tool to extend our understanding of how cells perceive, respond, and behave in meeting with complex signals, particularly in terms of cancer evasion from the anticancer immune system functions.

Recombinant production and characterization of L-glutaminase (glsA) as a promiscuity therapeutic enzyme.

Because of the therapeutical impacts of hydrolytic enzymes in different diseases, in particular malignancies, we aimed to produce a recombinant putative L-glutaminase (GLS ASL-1) from a recently characterized halo-thermotolerant Bacillus sp. SL-1. For this purpose, the glsA gene was identified and efficiently overexpressed in the Origami™ B (DE3) strain. The yield of the purified GLS ASL-1 was ~ 20 mg/L, indicating a significant expression of recombinant enzyme in the Origami. The enzyme activity assay revealed a significant hydrolytic effect of the recombinant GLS ASL-1 on L-asparagine (Asn) (i.e., Km 39.8 µM, kcat 19.9 S-1) with a minimal affinity for L-glutamine (Gln). The GLS ASL-1 significantly suppressed the growth of leukemic Jurkat cells through apoptosis induction (47.5%) in the IC50 dosage of the enzyme. The GLS ASL-1 could also change the Bax/Bcl2 expression ratio, indicating its apoptotic effect on cancer cells. The in silico analysis was conducted to predict structural features related to the histidine-tag exposure in the N- or C-terminal of the recombinant GLS ASL-1. In addition, molecular docking simulation for substrate specificity revealed a greater binding affinity of Asn to the enzyme binding-site residues than Gln, which was confirmed in experimental procedures as well. In conclusion, the current study introduced a recombinant GLS ASL-1 with unique functional and structural features, highlighting its potential pharmaceutical and medical importance. GLS ASL-1 represents the first annotated enzyme from Bacillus with prominent asparaginase activity, which can be considered for developing alternative enzymes in therapeutic applications. KEY POINTS: • Hydrolytic enzymes have critical applications in different types of human malignancies. • A recombinant L-glutaminase (GLS ASL-1) was produced from halo-thermotolerant Bacillus sp. SL-1. • GLS ASL-1 displayed a marked hydrolytic activity on L-asparagine compared to the L-glutamine. • GLS ASL-1 with significant substrate promiscuity may be an alternative for developing novel pharmaceuticals.

Multifunctional magnetic nanoparticles for MRI-guided co-delivery of erlotinib and L-asparaginase to ovarian cancer.

The use of magnetic nanoparticles (MNPs) in biomedical applications has been wildly opted due to their unique properties. Here, we designed MNPs loaded with erlotinib (ERL/SPION-Val-PEG) and conjugated them with anti-mucin16 (MUC16) aptamer to introduce new image-guided nanoparticles (NPs) for targeted drug delivery as well as non-invasive magnetic resonance imaging (MRI) contrast agents. Also, the combination of our nanosystem (NS) along with L-Asparaginase (L-ASPN) led to synergistic effects in terms of reducing cell viability in ovarian cancer cells, which could suggest a novel combination therapy. The mean size of our NS was about 63.4 ± 3.4 nm evaluated by DLS analysis and its morphology was confirmed using TEM. Moreover, the functional groups, as well as magnetic properties of our NS, were examined by FT-IR and VSM tests, respectively. The loading efficacy of erlotinib on MNPs was about 80% and its release reached 70.85% over 7 days in the pH value of 5.4. The MR images and flow cytometry results revealed that the cellular uptake of ERL/SPION-Val-PEG-MUC16 NPs in cells with MUC16 overexpression was considerably higher than unarmed NPs. In addition, T2-weight MR images of ovarian cancer-bearing mice indicated significant signal intensity changes at the tumour site 4 h after intravenous injection compared to the non-target MNPs. Our data suggest ERL/SPION-Val-PEG NPs as an image-guided co-drug delivery system for ovarian cancer.

Exosomes as versatile nanoscaled biocompartments in cancer therapy and/or resistance.

Cancer remains to be a major hurdle to global health. Exosomes as a versatile bio-derived platform, hold a bright prospect in nano-scaled delivery/targeting strategies. Shreds of evidence indicate that exosomes have a critical role in drug resistance in cancer cells through various mechanisms including shuttling of miRNAs, drug efflux transporters, and anti-apoptotic signaling. Exosomes' cargo, particularly miRNAs, may exert both resistance and in a few cases sensitivity to the anticancer agents in targeted cells. Therefore, the source and components of the exosomes should be carefully considered before any application. Our aim in this editorial is to further highlight the role of exosomes in the development of resistance to therapy in cancer cells. As a new chapter for drug delivery, the challenges should be elucidated before exosomes emerge as novel nanoplatforms for cancer therapy.

Synthesis and biological impacts of pollen shells/Fe3O4 nanoparticles composites on human MG-63 osteosarcoma cells.

INTRODUCTION: Cell-adhesive surfaces play a pivotal role in biomedical engineering, as most biological reactions take place on surfaces. Pollen shell (PSh) ofPistacia vera L., as a new medical device, has previously been reported to cause cytotoxicity and apoptosis in MG-63 bone cancer cells. METHODS: Iron oxide nanoparticles (Fe3O4NPs) were synthesized and their reaction to PShs was gauged at different concentrations, and then characterized using field emission scanning electron microscopy (FESEM), Fourier-transform infrared spectroscopy, energy dispersion X-ray spectrometer, X-ray diffraction spectra, dynamic light scattering, and vibrating sample magnetometer. Then, the biological impacts of PShs/Fe3O4NPs composites on MG-63 cells were investigated in-vitro using MTT assay, quantitative polymerase chain reaction (qPCR), Annexin V/propidium iodide, FESEM, and DAPI staining. RESULTS: Fe3O4NPs with a size range of 24-40 nm and a zeta potential value of -37.4 mV were successfully assembled on the PShs. The viability of MG-63 cells was significantly decreased when cultured on the magnetic PShs as compared to non-magnetic PShs, in Fe3O4 concentration and time-dependent manner. In contrast, magnetic PShs had a positive effect on the viability of normal human bone marrow-derived mesenchymal stem cells (hBM-MSCs). The analysis of apoptosis-related genes in cancer cells revealed that loading Fe3O4NPs on PShs increased expression of BAX/BCL2 and caspase-3 genes. The increased apoptotic activity of combined PShs/Fe3O4NPs was further confirmed by flow cytometric measurement, morphological analysis, and DAPI staining. CONCLUSION: The incorporation of Fe3O4NPs into PShs could effectively increase anticancer effects on MG-63 cells via the mitochondria-mediated apoptosis pathway, evident by upregulation of BAX/BCL2 ratio and caspase-3.

TEM1-targeting PEGylated PLGA shikonin nanoformulation for immunomodulation and eradication of ovarian cancer.

Introduction: Tumor endothelial marker 1 (TEM1) is expressed by tumor vascular endothelial cells in various cancers. Methods: Here, we developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) PEGylated with polyethylene glycol (PEG) and functionalized with anti-TEM1 antibody fragment (78Fc) and loaded them with necroptosis-inducing agent shikonin (SHK) (78Fc-PLGA-SHK NPs). Results: The nanoformulation showed a smooth spherical shape (~120 nm; the ζ potential of -30 mV) with high drug entrapment and bioconjugation efficiencies (~92% and ~90%, respectively) and a sustained-release profile in serum. Having significant toxicity in vitro (e.g., MS1 and TC1 cells), the nanoformulation dramatically increased the cytotoxicity in the TC1 murine lung carcinoma subcutaneous and intravenous/metastatic models as aggressive tumor models. The injection of the 78Fc-PLGA-SHK NPs to the MS1-xenograft mice resulted in significantly higher accumulation and effects in the TEM1-positive tumor targets, while they were excreted via urine track without retaining in the liver/spleen. In the TC1 subcutaneous model, C57/BL6 mice treated with the 78Fc-PLGA-SHK NPs revealed a significant therapeutic effect. The mice, which were tumor-free after receiving the nanoformulation, were re-challenged with the TC1 cells to investigate the immune response. These animals became tumor-free a week after the injection of TC1 cells. Conclusion: Based on these findings, we propose the 78Fc-PLGA-SHK NPs as a highly effective immunostimulating nanomedicine against the TEM1-expressing cells for targeted therapy of solid tumors including ovarian cancer.

Recent advances and trends in nanoparticles based photothermal and photodynamic therapy.

Light-mediated therapies, including photodynamic therapy (PDT) and photothermal therapy (PTT) have been exploited as minimally invasive techniques for ablation of various tumors., Both modalities may eradicate tumors with minimal side effects to normal tissues and organs. Moreover, developments of light-mediated approaches using nanoparticles (NPs) and photosensitizer (PS) as diagnostic and therapeutic agents may have a crucial role in achieving successful cancer treatment. In recent years, novel nanoplatforms and strategies have been investigated to boost the therapeutic effect.. In this regard, gold, iron oxide, graphene oxide nanoparticles and hybrid nanocomposites have attracted attention.. Moreover, the combination of these materials with PS, in the form of hybrid NPs, reduces in vitro and in vivo normal tissue cytotoxicity, improves their solubility property in the biological environment and enhances the therapeutic effects. In this review, we look into the basic principles of PTT and PDT with their strengths and limitations to treat cancers. We also will discuss light-based nanoparticles and their PTT and PDT applications in the preclinical and clinical translation. Also, recent advances and trends in this field will be discussed along with the clinical challenges of PTT and PDT.

Stimuli-responsive graphene oxide and methotrexate-loaded magnetic nanoparticles for breast cancer-targeted therapy.

Aim: Nanocomposites of graphene oxide (GO) loaded with PEGylated superparamagnetic iron oxide nanoparticles and grafted with methotrexate and stimuli-responsive linkers (GO-SPION-MTX) were developed for photothermal and chemotherapy of breast cancer. Methods: PEGylated SPIONs were synthesized and conjugated with chemotherapeutic targeting agent MTX, which were then loaded on GO to prepare GO-SPION-MTX nanocomposites. To evaluate the photothermal effect of the nanocomposites, they were examined in breast cancer cell lines with low doses of near-infrared (NIR) laser radiation with/without acetazolamide. Results: The GO-SPION-MTX nanocomposites were found to be internalized by the folate-receptor-positive cancer cells and induce high cytotoxicity on exposure to NIR laser rays. Conclusion: Our findings suggest that the GO-SPION-MTX nanocomposite can potentially be used as a multimodal nanomedicine/theranostic against breast cancer.

Folate receptor-mediated delivery of 1-MDT-loaded mesoporous silica magnetic nanoparticles to target breast cancer cells.

Aims: The efficiency of mesoporous silica magnetic nanoparticles (MSMNP) as a targeted drug-delivery system was investigated. Methods: The superparamagnetic iron oxide nanoparticles (NP) were synthesized, coated with mesoporous silica and conjugated with polyethylene glycol and methotrexate. Next, 1-methyl-D-tryptophan was loaded into the prepared nanosystems (NS). They were characterized using transmission electron microscopy, scanning electron microscopy, dynamic light scattering, vibrating sample magnetometer, x-ray powder diffraction, Fourier transform-infrared spectroscopy and the Brunauer-Emmett-Teller method and their biological impacts on breast cancer cells were evaluated. Results: The prepared NSs displayed suitable properties and showed enhanced internalization by folate-receptor-expressing cells, exerting efficient cytotoxicity, which was further enhanced by the near-infrared radiation irradiation. Conclusion: On the basis of our findings, the engineered NS is a promising multifunctional nanomedicine/theranostic for solid tumors.

Targeted combined therapy in 2D and 3D cultured MCF-7 cells using metformin and erlotinib-loaded mesoporous silica magnetic nanoparticles.

AIM: This research aims to develop potential therapeutic nanostructures (NSs) encapsulating metformin (MET) and erlotinib (ER) for combinational therapy in breast cancer. METHODS: The ER and MET, both were loaded on mesoporous silica magnetic nanoparticles conjugated with polyethylene glycol and methotrexate to achieve targeted NSs. The developed NSs were characterised using SEM, DLS, and FTIR. Afterward, MTT, Trypan blue, and DNA extraction assays were operated for biological evaluations in the 2D and 3D MCF-7 cells. RESULTS: Physicochemical approaches indicated the mean diameter of 69.4 nm ± 9.5 (PDI = 0.64), and neutral charge (2 mv) for the developed NSs. MET and ER-loaded NSs exhibited 62.56% ± 4.41 and 67.73% ± 3.03 drug release amount in pH = 5.4, respectively. MTT assay revealed that ER- and MET-loaded NSs had less metabolic activity (≈ 20%) in comparison with non-targeted NSs. CONCLUSION: Overall, our combined ER and MET-loaded targeted NSs result in a synergistic inhibitory impact on MCF-7 cells.

Progresses in polymeric nanoparticles for delivery of tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs), as an important class of chemotherapeutic drugs, induce apoptosis by altering the path of the cellular signal, resulting in cell death. However, some chemotherapeutic drugs have a limited therapeutic index and are usually destructive as well as unpredictable. In addition, the limitation of early diagnosis and inefficiency of some of the drugs in ordinary treatments lead to disease progression and decreases in the survival of cancer patients. For this purpose, various methods have been proposed, among them, nanomedicine has transpired as a modern approach for the treatment of multiple cancers. Over the last two decades, targeted therapy has been developed for cancer-specific cells/tissues and has rather restricted nonselective toxicities. In vivo and in vitro studies demonstrated nanoparticles (NPs), nano-scale drugs, and nano-carriers alone or in combination with other therapeutic, imaging, and theranostic agents would be applied as an effective approach targeting a diversity of malignant tissue. Therefore, using the latest advances in materials science and biomaterials, biology, it has happened that general diagnosis and treatment can be performed. In this review, we indicated the applications of theranostic nano-polymer and nano-liposome to TKIs delivery.

Role of cellulose family in fibril organization of collagen for forming 3D cancer spheroids: In vitro and in silico approach.

Introduction: Cell aggregation of three-dimensional (3D) culture systems (the so-called spheroids) are designed as in vitro platform to represent more accurately the in vivo environment for drug discovery by using semi-solid media. The uniform multicellular tumor spheroids can be generated based on the interaction of cells with extracellular matrix (ECM) macromolecules such as collagen and integrin. This study aimed to investigate the possible interactions between the cellulose family and collagen using both in vitro and in silico approaches. Methods: The 3D microtissue of JIMT-1 cells was generated using hanging drop method to study the effects of charge and viscosity of the medium containing cellulose family. To determine the mode of interaction between cellulose derivatives (CDs) and collagen-integrin, docking analysis and molecular simulation were further performed using open source web servers and chemical simulations (GROMACS), respectively. Results: The results confirmed that the addition of CDs into the 3D medium can promote the formation of solid spheroids, where methylcellulose (MC) yielded uniform spheroids compared to carboxymethyl cellulose (CMC). Moreover, the computational analysis showed that MC interacted with both integrin and collagen, while sodium carboxymethyl cellulose (NaCMC) only interacted with collagen residues. The stated different behaviors in the 3D culture formation and collagen interaction were found in the physicochemical properties of CDs. Conclusion: Based on in vitro and in silico findings, MC is suggested as an important ECM-mimicking entity that can support the semi-solid medium and promote the formation of the uniform spheroid in the 3D culture.

Recent advances in breast cancer immunotherapy: The promising impact of nanomedicines.

Breast cancer (BC) is one of the prevalent cancers among women. Generally, the treatment of BC is mostly based on several prominent strategies, including chemotherapy, surgery, endocrine therapy, molecular targeted therapy, and radiation. Owing to the growing knowledge about the complexity of BC pathobiology, immunotherapy as a promising treatment modality has substantially improved the patients' care in the clinic. Immunotherapy is used to harness the patient's immune system to recognize and battle devious cancer cells. As a novel therapy approach, this emerging strategy targets the key molecular entities of tumor tissue. To achieve maximal therapeutic impacts, the dynamic interplay between cancer and immune cells needs to be fully comprehended. The key molecular machinery of solid tumors can be targeted by nanoscale immunomedicines. While discussing the potential biomarkers involved in the initiation and progression of BC, we aimed to provide comprehensive insights into the immunotherapy and articulate the recent advances in terms of the therapeutic strategies used to control this disease, including immune checkpoint inhibitors, vaccines, chimeric antigen receptor T cells therapy, and nanomedicines.

Astaxanthin protects mesenchymal stem cells from oxidative stress by direct scavenging of free radicals and modulation of cell signaling.

Recent evidence has shown that mesenchymal stem cells (MSCs) play vital roles in cell therapy of ischemia/hypoxia damaged tissues. However, after the transplantation, they might undergo apoptosis due to oxidative stress. Thus, some strategies have been developed to support stem cells in harsh conditions, including pre-treatment of the cells with antioxidants. Of various antioxidants, in this study, astaxanthin (ATX) was used to protect adipose-derived MSCs against oxidative stress. The MSCs were exposed to different doses of hydrogen peroxide, and then the expression of key genes involved in the redox signaling pathway was studied, including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH quinine oxidoreductase 1 (NQO1). The balance of intracellular reactive oxygen species was detected with the H2DCFDA molecular probe. Additionally, for the detection of apoptosis and protective effect of ATX, the DAPI/Phallacidin and annexin V cell staining were performed. The results of cellular studies revealed that ATX reduced the H2O2-induced cell apoptosis and oxidative stress. Furthermore, after the induction of oxidative stress, the cells' native antioxidants (HO-1 and NQO1) were overexpressed but they were modulated with ATX treatments (p < 0.023). Based on our findings, ATX could increase the expression of Nrf2 as a key transcription factor of antioxidant enzymes (p < 0.05). These findings support the notion that ATX can act as an effective antioxidant in the pre-treatment of MSCs before cell therapy. Thus, to enhance the viability of stem cells during the transplantation in harsh conditions, the concurrent use of ATX in cell therapy modalities is proposed.

Smart stimuli-responsive biopolymeric nanomedicines for targeted therapy of solid tumors.

Solid tumors form a permissive microenvironment with irregular features, including high pressured tumor interstitial fluid with acidic pH, co-adaptation of cancer cells with other cells like the immune system cells, abnormal metabolism and anomalous overexpression of various pieces of molecular machinery. The functional expressions of several oncomarkers in different solid tumors have led to the development of targeted drug-delivery systems (DDSs). As a new class of DDSs, stimuli-responsive nanomedicines (SRNMs) have been developed using advanced nanobiomaterials such as biopolymers that show excellent biocompatibility with low inherent immunogenicity. In this review, we aim to overview different types of SRNMs, present deep insights into the stimuli-responsive biopolymers and discuss the most up-to-date progress in the design and development of SRNMs used as advanced DDSs for targeted therapy of cancer.