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.

Recent advances in targeted drug delivery systems for resistant colorectal cancer.

Colorectal cancer (CRC) is one of the deadliest cancers in the world, the incidences and morality rate are rising and poses an important threat to the public health. It is known that multiple drug resistance (MDR) is one of the major obstacles in CRC treatment. Tumor microenvironment plus genomic instability, tumor derived exosomes (TDE), cancer stem cells (CSCs), circulating tumor cells (CTCs), cell-free DNA (cfDNA), as well as cellular signaling pathways are important issues regarding resistance. Since non-targeted therapy causes toxicity, diverse side effects, and undesired efficacy, targeted therapy with contribution of various carriers has been developed to address the mentioned shortcomings. In this paper the underlying causes of MDR and then various targeting strategies including exosomes, liposomes, hydrogels, cell-based carriers and theranostics which are utilized to overcome therapeutic resistance will be described. We also discuss implication of emerging approaches involving single cell approaches and computer-aided drug delivery with high potential for meeting CRC medical needs.

Bioactive polymeric scaffolds for osteogenic repair and bone regenerative medicine.

The loss of bone tissue is a striking challenge in orthopedic surgery. Tissue engineering using various advanced biofunctional materials is considered a promising approach for the regeneration and substitution of impaired bone tissues. Recently, polymeric supportive scaffolds and biomaterials have been used to rationally promote the generation of new bone tissues. To restore the bone tissue in this context, biofunctional polymeric materials with significant mechanical robustness together with embedded materials can act as a supportive matrix for cellular proliferation, adhesion, and osteogenic differentiation. The osteogenic regeneration to replace defective tissues demands greater calcium deposits, high alkaline phosphatase activity, and profound upregulation of osteocalcin as a late osteogenic marker. Ideally, the bioactive polymeric scaffolds (BPSs) utilized for bone tissue engineering should impose no detrimental impacts and function as a carrier for the controlled delivery and release of the loaded molecules necessary for the bone tissue regeneration. In this review, we provide comprehensive insights into different synthetic and natural polymers used for the regeneration of bone tissue and discuss various technologies applied for the engineering of BPSs and their physicomechanical properties and biological effects.

Overexpression of CFL1 in gastric cancer and the effects of its silencing by siRNA with a nanoparticle delivery system in the gastric cancer cell line.

Gastric adenocarcinoma, like other cancers, is a multifactorial genetic disease, and metastasis of cancer cells is one of the main features of this illness. The expression levels of the CFL1 gene have been modulated in this pathway. Using small interfering RNA (siRNA) in the treatment of gastric cancer is considered a hopeful gene therapeutic approach. The present study reported the level of CFL1 genes between tumor and margin and healthy tissue of gastric cancer. Also, the features of a cationic nanoparticle with a polymer coating containing polyacrylic acid and polyethyleneimine that were used in the delivery of CFL1 siRNA, were shown. Then the cytotoxicity, cellular uptake, and gene silencing efficiency of this nanoparticle were evaluated with CFL1siRNA. METHOD: In this study, the CFL1 gene expression was measured in 40 gastric adenocarcinoma, marginal and 15 healthy biopsy samples by a real-time polymerase chain reaction. Physicochemical characteristics, apoptosis, and inhibition of migration of the delivery of CFL1 siRNA by nanoparticle and lipofectamine were investigated in gastric cancer cells. RESULT: The CFL1 expression was remarkably increased in gastric cancer tissues in comparison with the marginal samples and normal tissues (p < .05) and the biomarker index for CFL1 was obtained as 0.94, then this gene can be probably used as a biomarker for gastric cancer. After treatment of the AGS cell line by CFL1 siRNA, the CFL1 expression level of mRNA and migration in AGS cells were remarkably suppressed after transfection. Furthermore, the amount of apoptosis increased (p < .05). CONCLUSION: Our results demonstrated that CFL1 downregulation in AGS cells can interdict cell migration. Finally, our outcomes propose that CFL1 can function as an oncogenic gene in gastric cancer and would be considered as a potential purpose of gene therapy for gastric cancer treatment.

Chitosan-based multifunctional nanomedicines and theranostics for targeted therapy of cancer.

Nanotechnology as an emerging field has established inevitable impacts on nano-biomedicine and treatment of formidable diseases, inflammations, and malignancies. In this regard, substantial advances in the design of systems for delivery of therapeutic agents have emerged magnificent and innovative pathways in biomedical applications. Chitosan (CS) is derived via deacetylation of chitin as the second most abundant polysaccharide. Owing to the unique properties of CS (e.g., biocompatibility, biodegradability, bioactivity, mucoadhesion, cationic nature and functional groups), it is an excellent candidate for diverse biomedical and pharmaceutical applications such as drug/gene delivery, transplantation of encapsulated cells, tissue engineering, wound healing, antimicrobial purposes, etc. In this review, we will document, discuss, and provide some key insights toward design and application of miscellaneous nanoplatforms based on CS. The CS-based nanosystems (NSs) can be employed as advanced drug delivery systems (DDSs) in large part due to their remarkable physicochemical and biological characteristics. The abundant functional groups of CS allow the facile functionalization in order to engineer multifunctional NSs, which can simultaneously incorporate therapeutic agents, molecular targeting, and diagnostic/imaging capabilities in particular against malignancies. These multimodal NSs can be literally translated into clinical applications such as targeted diagnosis and therapy of cancer because they offer minimal systemic toxicity and maximal cytotoxicity against cancer cells and tumors. The recent developments in the CS-based NSs functionalized with targeting and imaging agents prove CS as a versatile polymer in targeted imaging and therapy.

Novel polyacrylate-based cationic nanoparticles for survivin siRNA delivery combined with mitoxantrone for treatment of breast cancer.

As a gene delivery method in breast cancer therapy, knocking down the undesired genes in the cancerous cells would be promising. Inhibitors of Apoptosis Protein (IAP) family genes are some of the genes whose responsibility is inhibition of apoptosis in cells. Silencing these genes seems to be helpful directing the tumor cells to death. siRNA sequence designed against survivin anti-apoptotic gene can play this role if carried to the cytoplasm. Here we prepared a positive charged biocompatible nano-sized particle made up of a Fe3O4 core covered respectively by polyacrylate (PA) and polyethyleneimine (PEI) layer, which could successfully deliver the siRNA into the MCF-7 cells. The particle structure was checked and having less than 50 nm diameter in size, positive charge and, safety towards MCF-7 cells besides being able to form nanoplexes with the siRNA strand helps it entering into the biologic assays part. The siRNA delivery evaluated via flowcytometry. Apoptosis induction was determined by DAPI staining. The efficiency of survivin gene knockdown was evaluated in mRNA and protein levels using Real time PCR and western blotting methods. Overall, the Fe3O4-PA-PEI nanoparticles can deliver siRNA effectively into the cytoplasm of the MCF-7 breast cancer cells and induce apoptosis.

Bioscaffolds of graphene based-polymeric hybrid materials for myocardial tissue engineering.

Introduction: Biomaterials currently utilized for the regeneration of myocardial tissue seem to associate with certain restrictions, including deficiency of electrical conductivity and sufficient mechanical strength. These two factors play an important role in cardiac tissue engineering and regeneration. The contractile property of cardiomyocytes depends on directed signal transmission over the electroconductive systems that happen inside the innate myocardium. Because of their distinctive electrical behavior, electroactive materials such as graphene might be used for the regeneration of cardiac tissue. Methods: In this review, we aim to provide deep insight into the applications of graphene and graphene derivative-based hybrid polymeric scaffolds in cardiomyogenic differentiation and cardiac tissue regeneration. Results: Synthetic biodegradable polymers are considered as a platform because their degradation can be controlled over time and easily functionalized. Therefore, graphene-polymeric hybrid scaffolds with anisotropic electrical behavior can be utilized to produce organizational and efficient constructs for macroscopic cardiac tissue engineering. In cardiac tissue regeneration, natural polymer based-scaffolds such as chitosan, gelatin, and cellulose can provide a permissive setting significantly supporting the differentiation and growth of the human induced pluripotent stem cells -derived cardiomyocytes, in large part due to their negligible immunogenicity and suitable biodegradability. Conclusion: Cardiac tissue regeneration characteristically utilizes an extracellular matrix (scaffold), cells, and growth factors that enhance cell adhesion, growth, and cardiogenic differentiation. From the various evaluated electroactive polymeric scaffolds for cardiac tissue regeneration in the past decade, graphene and its derivatives-based materials can be utilized efficiently for cardiac tissue engineering.

In situ forming alginate/gelatin hydrogel scaffold through Schiff base reaction embedded with curcumin-loaded chitosan microspheres for bone tissue regeneration.

In this study, we developed a biocompatible composite hydrogel that incorporates microspheres. This was achieved using a Schiff base reaction, which combines the amino and aldehyde groups present in gelatin (Gel) and oxidized alginate (OAlg). We suggest this hydrogel as a promising scaffold for bone tissue regeneration. To further boost its osteogenic capabilities and mechanical resilience, we synthesized curcumin (Cur)-loaded chitosan microspheres (CMs) and integrated them into the Gel-OAlg matrix. This formed a robust composite gel framework. We conducted comprehensive evaluations of various properties, including gelation time, morphology, compressive strength, rheological behavior, texture, swelling rate, in vitro degradation, and release patterns. A remarkable observation was that the inclusion of 30 mg/mL Cur-CMs significantly enhanced the hydrogel's mechanical and bioactive features. Over three weeks, the Gel-OAlg/Cur-CMs (30) composite showed a cumulative curcumin release of 35.57%. This was notably lower than that observed in standalone CMs and Gel-OAlg hydrogels. Additionally, the Gel-OAlg/Cur-CMs (30) hydrogel presented a reduced swelling rate and weight loss relative to hydrogels devoid of Cur-CMs. On the cellular front, the Gel-OAlg/Cur-CMs (30) hydrogel showcased superior biocompatibility. It also displayed increased calcium deposition, alkaline phosphatase (ALP) activity, and elevated osteogenic gene expression in human bone marrow mesenchymal stem cells (hBMSCs). These results solidify its potential as a scaffold for bone tissue regeneration.

Niosomes containing paclitaxel and gold nanoparticles with different coating agents for efficient chemo/photothermal therapy of breast cancer.

Breast cancer (BC) is one of the most common cancers in women, and chemotherapy is usually used to overcome this cancer. To improve drug delivery to cancer sites and reduce their side effects, nanocarriers such as niosomes (NIOs) are used. Moreover, a combination of other therapeutic methods like photothermal therapy (PTT) can help to enhance the chemotherapy effect. The aim of this research is the design a nanocarrier that simultaneously delivers chemotherapy and PTT agents. To achieve this goal, NIOs containing paclitaxel (PTX) as a chemotherapeutic agent and spherical gold nanoparticles (AuNPs) coated with citrate, chitosan (CS), and polyamidoamine (PAMAM) as a PTT agent were synthesized by thin hydration methods. Their physicochemical properties were determined by dynamic light scattering, UV-Vis, Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) analysis. Cellular uptake, cell cytotoxicity, hyperthermia, and apoptosis effects of the proposed system were investigated in the MCF-7 BC cell line. The cellular uptake of NIOs/AuNPs-PAMAM (99.21%) and NIOs/AuNPs-CS (98.93%) by MCF-7 cells was higher than that of NIOs/AuNPs (79.55%), demonstrating that surface charge plays a key role in the cellular uptake of NPs. The MTT assay showed the cell viability of 45.48% for NIOs/AuNPs/PTX, 34.24% for NIOs/AuNPs-CS/PTX, and 37.67% for NIOs/AuNPs-PAMAM/PTX after 48 h of treatment. However, the application of hyperthermia significantly decreased the viability of cells treated with NIOs/AuNPs/PTX (37.72%), NIOs/AuNPs-CS/PTX (10.49%), and NIOs/AuNPs-PAMAM/PTX (4.1%) after 48 h. The apoptosis rate was high in NIOs/AuNPs-PAMAM/PTX (53.24%) and NIOs/AuNPs-CS/PTX (55.4%) confirming the data from MTT. In conclusion, the result revealed that combined PTT with chemotherapy increased cell cytotoxicity effects against the MCF-7 cells, and the AuNPs with various coating agents affected cellular uptake and hyperthermia which can be considered for efficient BC therapy.

Codelivery of methotrexate and silibinin by niosome nanoparticles for enhanced chemotherapy of CT26 colon cancer cells.

Colon cancer (CC) is one of the most prevalent cancers in the world, and chemotherapy is widely applied to combat it. However, chemotherapy drugs have severe side effects and emergence of multi drug resistance (MDR) is common. This bottleneck can be overcome by niosome nanocarriers that minimize drug dose/toxicity meanwhile allow co-loading of incompatible drugs for combination therapy. In this research, silibinin (Sil) as a hydrophobic drug was loaded into the lipophilic part, and methotrexate (MTX) into the hydrophilic part of niosome by the thin film hydration (TFH) method to form Nio@MS NPs for CT26 colon cancer therapy in vitro. Our results indicated synthesis of ideal niosome nanoparticles (NPs) with spherical morphology, size of ~100 nm, and a zeta potential of -10 mV. The IC50 value for Nio@MS was determined ~2.6 µg/mL, which was significantly lower than MTX-Sil (~6.86 µg/mL), Sil (18.46 µg/mL), and MTX (9.8 µg/mL). Further, Nio@MS significantly reduced cell adhesion density, promoted apoptosis and increased gene expression level of caspase 3 and BAX while promoted significant downregulation of BCL2. In conclusion, the design and application of niosome to co-administer Sil and MTX can increase the drugs cytotoxicity, reduce their dose and improve anti-cancer potential by combating MDR. .

Hyaluronic Acid-Targeted Niosomes for Effective Breast Cancer Chemostarvation Therapy.

Chemotherapy is widely used for cancer therapy; however, its efficacy is limited due to poor targeting specificity and severe side effects. Currently, the next generations of delivery systems with multitasking potential have attracted significant attention for cancer therapy. This study reports on the design and synthesis of a multifunctional nanoplatform based on niosomes (NIO) coloaded with paclitaxel (PTX), a chemotherapeutic drug commonly used to treat breast cancer, and sodium oxamate (SO), a glycolytic inhibitor to enhance the cytotoxicity of anticancer drug, along with quantum dots (QD) as bioimaging agents, and hyaluronic acid (HA) coating for active targeting. HN@QPS nanoparticles with a size of ∼150 nm and a surface charge of -39.9 mV with more than 90% EE for PTX were synthesized. Codelivery of SO with PTX remarkably boosted the anticancer effects of PTX, achieving IC50 values of 1-5 and >0.5 ppm for HN@QP and HN@QPS, respectively. Further, HN@QPS treatment enhanced the apoptosis rate by more than 70% in MCF-7 breast cancer cells without significant cytotoxicity on HHF-2 normal cells. Also, quantification of mitochondrial fluorescence showed efficient toxicity against MCF-7 cells. Moreover, the cellular uptake evaluation demonstrated an improved uptake of HN@Q in MCF-7 cells. Taken together, this preliminary research indicated the potential of HN@QPS as an efficient targeted-dual drug delivery nanotheranostic against breast cancer cells.

Discovering therapeutic possibilities for polycystic ovary syndrome by targeting XIST and its associated ceRNA network through the analysis of transcriptome data.

Long non-coding RNA (lncRNA) regulates many physiological processes by acting as competitive endogenous RNA (ceRNA). The dysregulation of lncRNA X-inactive specific transcript (XIST) has been shown in various human disorders. However, its role in the pathogenesis of polycystic ovary syndrome (PCOS) is yet to be explored. This study aimed to explore the underlying mechanism of XIST in the pathogenesis of PCOS, specifically through dataset functional analysis. GEO PCOS datasets including RNA-seq, microarray, and miRNA-seq in granulosa cells (GCs) and blood, were examined and comprehensively analyzed. Enrichment analysis, ROC curve constructions, lncRNA-miRNA-mRNA interaction network analyses, and qRT-PCR validation were performed followed by a series of drug signature screenings. Our results revealed significant dysregulation in the expression of 1131 mRNAs, 30 miRNAs, and XIST in GCs of PCOS patients compared to healthy individuals. Of the120 XIST-correlated upregulated genes, 25 were enriched in inflammation-related pathways. Additionally, 5 miRNAs were identified as negative regulators of XIST-correlated genes. Accordingly, a ceRNA network containing XIST-miRNAs-mRNAs interactions was constructed. Furthermore, 6 genes, including AQP9, ETS2, PLAU, PLEK, SOCS3, and TNFRSF1B served as both GCs and blood-based biomarkers. By analyzing the number of interactions among XIST, miRNAs, and mRNAs, we pinpointed ETS2 as the pivotal gene within the ceRNA network. Our findings reveal a novel XIST- hsa-miR-146a-5p, hsa-miR-144-3p, and hsa-miR-1271-5p-ETS2 axis that comprehensively elucidates the XIST-associated mechanism underlying PCOS onset. qRT-PCR analysis further confirmed the, overexpression of both XIST and ETS2 . Furthermore, our results demonstrated that XIST and ETS2 were correlated with some assisted reproductive technologies outcomes. Finally, we identified two novel compounds including, methotrexate/folate and threonine using drug-gene interaction databases for PCOS management. These findings provide novel insights into the molecular etiology, diagnosis, and potential therapeutic interventions for PCOS.

In situ forming alginate/gelatin hybrid hydrogels containing doxorubicin loaded chitosan/AuNPs nanogels for the local therapy of breast cancer.

In this study, pH-sensitive in situ gelling hydrogels based on oxidized alginate and gelatin-containing doxorubicin (DOX) loaded chitosan/gold nanoparticles (CS/AuNPs) nanogels were fabricated via Schiff-base bond formation. The obtained CS/AuNPs nanogels indicated a size distribution of about 209 nm with a zeta potential of +19.2 mV and an encapsulation efficiency of around 72.6 % for DOX. The study of the rheological properties of hydrogels showed that the value of G' is higher than G″ for all hydrogels, which confirms the elastic behavior of hydrogels in the applied frequency range. The rheological and texture analysis demonstrated the higher mechanical properties of hydrogels containing ß-GP and CS/AuNPs nanogels. The release profile of DOX after 48 h indicates the 99 % and 73 % release amount at pH = 5.8 and pH = 7.4, respectively. MTT cytotoxicity study showed that the prepared hydrogels are cytocompatible on MCF-7 cells. By the Live/Dead assay, it was demonstrated that the cultured cells on DOX-free hydrogels were almost alive in the presence of CS/AuNPs nanogels. However, the hydrogel-containing drug and free DOX in the same concentration caused high death of MCF-7 cells as expected, which showed the potential of the developed hydrogels for application in the local treatment of breast cancer.

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 silibinin via magnetic niosomal nanoparticles: potential application in treatment of colon cancer cells.

Introduction: In recent years, various nanoparticles (NPs) have been discovered and synthesized for the targeted therapy of cancer cells. Targeted delivery increases the local concentration of therapeutics and minimizes side effects. Therefore, NPs-mediated targeted drug delivery systems have become a promising approach for the treatment of various cancers. As a result, in the current study, we aimed to design silibinin-loaded magnetic niosomes nanoparticles (MNNPs) and investigate their cytotoxicity property in colorectal cancer cell treatment. Methods: MNPs ferrofluids were prepared and encapsulated into niosomes (NIOs) by the thin film hydration method. Afterward, the morphology, size, and chemical structure of the synthesized MNNPs were evaluated using the TEM, DLS, and FT-IR techniques, respectively. Results and Discussion: The distribution number of MNNPs was obtained at about 50 nm and 70 nm with a surface charge of -19.0 mV by TEM and DLS analysis, respectively. Silibinin loading efficiency in NIOs was about 90%, and the drug release pattern showed a controlled release with a maximum amount of about 49% and 70%, within 4 h in pH = 7.4 and pH = 5.8, respectively. To investigate the cytotoxicity effect, HT-29 cells were treated with the various concentration of the drugs for 24 and 48 h and evaluated by the MTT as well as flow cytometry assays. Obtained results demonstrated promoted cell cytotoxicity of silibinin-loaded MNNPs (5-fold decrease in cell viability) compared to pure silibinin (3-fold decrease in cell viability) while had no significant cytotoxic effect on HEK-293 (normal cell line) cells, and the cellular uptake level of MNNPs by the HT-29 cell line was enhanced compared to the control group. In conclusion, silibinin-loaded MNNPs complex can be considered as an efficient treatment approach for colorectal cancer cells.

Molecular targets, therapeutic agents and multitasking nanoparticles to deal with cancer stem cells: A narrative review.

There is increasing evidence that malignant tumors are initiated and maintained by a sub-population of tumor cells that have similar biological properties to normal adult stem cells. This very small population of Cancer Stem Cells (CSC) comprises tumor initiating cells responsible for cancer recurrence, drug resistance and metastasis. Conventional treatments such as chemotherapy, radiotherapy and surgery, in addition to being potentially toxic and non-specific, may paradoxically increase the population, spread and survival of CSCs. Next-generation sequencing and omics technologies are increasing our understanding of the pathways and factors involved in the development of CSCs, and can help to discover new therapeutic targets against CSCs. In addition, recent advances in nanomedicine have provided hope for the development of optimal specific therapies to eradicate CSCs. Moreover, the use of artificial intelligence and nano-informatics can elucidate new drug targets, and help to design drugs and nanoparticles (NPs) to deal with CSCs. In this review, we first summarize the properties of CSCs and describe the signaling pathways and molecular characteristics responsible for the emergence and survival of CSCs. Also, the location of CSCs within the tumor and the effect of host factors on the creation and maintenance of CSCs are discussed. Newly discovered molecular targets involved in cancer stemness and some novel therapeutic compounds to combat CSCs are highlighted. The optimum properties of anti-CSC NPs, including blood circulation and stability, tumor accumulation and penetration, cellular internalization, drug release, endosomal escape, and aptamers designed for specific targeting of CSCs are covered. Finally, some recent smart NPs designed for therapeutic and theranostic purposes to overcome CSCs are discussed.

Injectable thermosensitive chitosan/gelatin hydrogel for dental pulp stem cells proliferation and differentiation.

Introduction: Biocompatible and biodegradable scaffolds based on natural polymers such as gelatin and chitosan (CS) provide suitable microenvironments in dental tissue engineering. In the present study, we report on the synthesis of injectable thermosensitive hydrogel (PNIPAAm-g-CS copolymer/gelatin hybrid hydrogel) for osteogenic differentiation of human dental pulp stem cells (hDPSCs). Methods: The CS-g-PNIPAAm was synthesized using the reaction of carboxyl terminated PNIPAAm with CS, which was then mixed with various amounts of gelatin solution in the presence of genipin as a chemical crosslinker to gain a homogenous solution. The chemical composition and microstructures of the fabricated hydrogels were confirmed by FT-IR and SEM analysis, respectively. To evaluate the mechanical properties (e.g., storage and loss modulus of the gels), the rheological analysis was considered. Calcium deposition and ALP activity of DPSCs were carried out using alizarin red staining and ALP test. While the live/dead assay was performed to study its toxicity, the real-time PCR was conducted to investigate the osteogenic differentiation of hDPSCs cultured on prepared hydrogels. Results: The hydrogels with higher gelatin incorporation showed a slightly looser network compared to the other ones. The hydrogel with less gelatin indicates a rather higher value of G', indicating a higher elasticity due to more crosslinking reaction of amine groups of CS via a covalent bond with genipin. All the hydrogels contained viable cells with negligible dead cells, indicating the high biocompatibility of the prepared hydrogels for hDPSCs. The quantitative results of alizarin red staining displayed a significant rise in calcium deposition in hDPSCs cultured on prepared hydrogels after 21 days. Further, hDPSCs cultured on hydrogel with more gelatin displayed the most ALP activity. The expression of late osteogenic genes such as OCN and BMP-2 were respectively 6 and 4 times higher on the hydrogel with more gelatin than the control group after 21 days. Conclusion: The prepared PNIPAAm-g-CS copolymer/gelatin hybrid hydrogel presented great features (e.g., porous structure, suitable rheological behavior, and improved cell viability), and resulted in osteogenic differentiation necessary for dental tissue engineering.

Using physicochemical and biological parameters for the evaluation of water quality and environmental conditions in international wetlands on the southern part of Lake Urmia, Iran.

The Kani Barazan and Yadegarlou wetlands in the southern part of Lake Urmia (Iran) have been substantially modified due to human activities and anthropogenic use. In recent years, freshwater-based eco-biological studies to recognize the quality of water resources have been greatly expanded. Microalgae and Cyanophyta are considered important bioindicators for the evaluation of water quality and wetland health worldwide. Herein, 22 microalgae and 5 Cyanophyta genera were identified in both wetlands, in which Cyanophyta has mainly caused blooms. Principal components analysis (PCA) was carried out based on links between the distribution of microalgae and Cyanophyta with physical and chemical parameters. The data showed that depth, turbidity, and the temperature had a significant influence on the microalga and Cyanophyta communities in both wetlands. Based on the biological properties, it seems that the Kani Barazan and Yadegarlou international wetlands experience meso-eutrophic conditions. The integration of the physical, chemical and biological parameters with the water quality index (WQI) revealed that both wetlands were polluted as a consequence of human activities. Moreover, a close relationship between WQI and the biological parameters was documented. Thus, we concluded that microalgae and Cyanophyta communities, their abundance patterns, and water quality changes could provide valuable data for the conservation of the Kani Barazan and Yadegarlou international wetlands.

Designing robust chitosan-based hydrogels for stem cell nesting under oxidative stress.

Introduction: Hydrogels are unique candidates for a wide range of biomedical applications including drug delivery and tissue engineering. The present investigation was designed to consider the impact of chitosan-based hydrogels as a scaffold on the proliferation of human bone marrow mesenchymal stem cells (hBM-MSCs) besides neutralization of oxidative stress in hBM-MSCs. Methods: Chitosan (CS) and CS-gelatin hydrogels were fabricated through ionic crosslinking using ß-glycerophosphate. The hBM-MSCs were cultured on the prepared matrices and their proliferation was evaluated using DAPI staining and MTT assay. Furthermore, the effect of hydrogels on oxidative stress was assessed by measuring the expression of NQO1, Nrf2, and HO-1 genes using real-time PCR. Results: The developed hydrogels indicated a porous structure with high water content. The toxicity studies showed that the prepared hydrogels have a high biocompatibility/cytocompatibility. The expression of intracellular antioxidant genes was studied to ensure that stress is not imposed by the scaffold on the nested cells. The results showed that Nrf2 as a super transcription factor of antioxidant genes and its downstream antioxidant gene, NQO1 were downregulated. Unexpectedly, the upregulation of HO-1 was detected in the current study. Conclusion: The prepared CS-based hydrogels with desired properties including porous structure, high swelling ability, and cytocompatibility did not show oxidative stress for the nesting of stem cells. Therefore, they could be attractive scaffolds to support stem cells for successful tissue engineering purposes.

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.