Chitosan-stabilized Selenium Nanoparticles Research Articles

Microwave synthesis of Chitosan-stabilized selenium nanoparticles: Intrinsic oxidant scavenging capabilities, hemocompatibility, anticancer, and antibacterial potency

Chitosan-stabilized selenium nanoparticles (Ch-St-SeNPs) were produced using Chitosan (Ch) in conjunction with microwave technology. Based on the morphological analysis, it was determined that the Ch-St-SeNPs were spherical and had sizes that varied between 8.0 and 17.0 nm. In addition, the DPPH radical scavenging test was conducted to evaluate the antioxidant effectiveness. The results showed that the green nanoparticle, prepared at 100.0 mg/mL, exhibited the highest scavenging capacity (297.1 ± 10.2 mg g−1). The concentrations of Ch-St-SeNPs reach 500 mg/ml, and the in-vitro cell viability of Ch-St-SeNPs via human breast cancer MCF-7 cell lines will decrease to 41.2 ± 3.1 % within a day of exposure. The evaluation of Ch-St-SeNPs included an analysis of their hemolytic strength, which was found to be significant. According to the findings, Ch-St-SeNPs exhibited excellent results, with no noticeable effect on RBCs and a considerably lower toxicity rate (7.2 %) compared to Triton-X-100, which showed a toxicity rate of 98.1 %. The effectiveness of Ch-St-SeNPs was evaluated by testing its antibacterial properties against various types of bacteria, including Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis). Results showed thatCh-St-SeNPs had a more significant impact on E. coli with a ZOI of 23.2 ± 1.3 mm compared to the standard antibiotic, which only had a ZOI of 15.0 ± 0.7 mm. According to prior research, Ch-St-SeNPs have potential applications in healthcare due to their ability as anticancer, antioxidants, and impact bacteria. In addition, the compatibility of human red blood cells is also a factor to consider.

Unraveling the Mechanisms of Ch-SeNP Cytotoxicity against Cancer Cells: Insights from Targeted and Untargeted Metabolomics.

Although chitosan-stabilized selenium nanoparticles (Ch-SeNPs) have emerged as a promising chemical form of selenium for anticancer purposes, gathering more profound knowledge related to molecular dysfunctions contributes significantly to the promotion of their evolution as a chemotherapeutic drug. In this sense, metabolites are the end products in the flow of gene expression and, thus, the most sensitive to changes in the physiological state of a biological system. Therefore, metabolomics provides a functional readout of the biochemical activity and cell state. In the present study, we evaluated alterations in the metabolomes of HepG2 cells after the exposure to Ch-SeNPs to elucidate the biomolecular mechanisms involved in their therapeutic effect. A targeted metabolomic approach was conducted to evaluate the levels of four of the main energy-related metabolites (adenosine triphosphate (ATP); adenosine diphosphate (ADP); nicotinamide adenine dinucleotide (NAD+); and 1,4-dihydronicotinamide adenine dinucleotide (NADH)), revealing alterations as a result of exposure to Ch-SeNPs related to a shortage in the energy supply system in the cell. In addition, an untargeted metabolomic experiment was performed, which allowed for the study of alterations in the global metabolic profile as a consequence of Ch-SeNP exposure. The results indicate that the TCA cycle and glycolytic pathways were impaired, while alternative pathways such as glutaminolysis and cysteine metabolism were upregulated. Additionally, increased fructose levels suggested the induction of hypoxia-like conditions. These findings highlight the potential of Ch-SeNPs to disrupt cancer cell metabolism and provide insights into the mechanisms underlying their antitumor effects.

Osteogenic and anti-inflammatory effects of SLA titanium substrates doped with chitosan-stabilized selenium nanoparticles via a covalent coupling strategy

Osseointegration is a prerequisite for the function of dental implants, and macrophage-dominated immune responses triggered by implantation determine the outcome of ultimate bone healing mediated by osteogenic cells. The present study aimed to develop a modified titanium (Ti) surface by covalently immobilizing chitosan-stabilized selenium nanoparticles (CS-SeNPs) to sandblasted, large grit, and acid-etched (SLA) Ti substrates and further explore its surface characteristics as well as osteogenic and anti-inflammatory activities in vitro. CS-SeNPs were successfully prepared by chemical synthesis and characterized their morphology, elemental composition, particle size, and Zeta potential. Subsequently, three different concentrations of CS-SeNPs were loaded to SLA Ti substrates (Ti-Se1, Ti-Se5, and Ti-Se10) using a covalent coupling strategy, and the SLA Ti surface (Ti-SLA) was used as a control. Scanning electron microscopy images revealed different amounts of CS-SeNPs, and the roughness and wettability of Ti surfaces were less susceptible to Ti substrate pretreatment and CS-SeNP immobilization. Besides, X-ray photoelectron spectroscopy analysis showed that CS-SeNPs were successfully anchored to Ti surfaces. The results of in vitro study showed that the four as-prepared Ti surfaces exhibited good biocompatibility, with Ti-Se1 and Ti-Se5 groups showing enhanced adhesion and differentiation of MC3T3-E1 cells compared with the Ti-SLA group. In addition, Ti-Se1, Ti-Se5, and Ti-Se10 surfaces modulated the secretion of pro-/anti-inflammatory cytokines by inhibiting the nuclear factor kappa B pathway in Raw 264.7 cells. In conclusion, doping SLA Ti substrates with a modest amount of CS-SeNPs (1–5 mM) may be a promising strategy to improve the osteogenic and anti-inflammatory activities of Ti implants.

Selenium Nanoparticles (SeNPs) Immunomodulation Is More Than Redox Improvement: Serum Proteomics and Transcriptomic Analyses.

Selenium nanoparticles (SeNPs) are a novel elemental form selenium and often reported to possess beneficial bioactivities such as anticancer, promoting bone growth and immunomodulation. Our previous study demonstrated that chitosan-stabilized SeNPs have strong activity in immunomodulation. However, the mechanism underlying the immunomodulation of SeNPs is still unknown. The aim of this study is to identify the molecular mechanisms involved in SeNP-induced immunomodulation. Using zebrafish, as a common immunological animal model with a highly conserved molecular mechanism with other vertebrates, we conducted serum proteomic and tissue transcriptome analyses on individuals fed with SeNP in healthy or disease conditions. We also compared differences between SeNPs and an exogenous antioxidant Trolox in immune activity and redox regulation. Our results suggest that the immunomodulation activity was highly related to antioxidant activity and lipid metabolism. Interestingly, the biological functions enhanced by SeNP were almost identical in the healthy and disease conditions. However, while the SeNP was suppressing ROS in healthy individuals, it promoted ROS formation during disease condition. This might be related to the defense mechanism against pathogens. SOD and NFkβ appeared to be the key molecular switch changing effect of SeNPs when individuals undergo infection, indicating the close relationship between immune and redox regulation.

Transcriptome Analysis Identifies Novel Mechanisms Associated with the Antitumor Effect of Chitosan-Stabilized Selenium Nanoparticles.

Selenium nanoparticles (SeNPs) have been receiving special attention in recent years due to their antioxidant capacity and antitumor properties. However, the mechanisms associated with these properties remain to be elucidated. For this reason, a global transcriptome analysis has been designed in this work and it was carried out using human hepatocarcinoma cells and chitosan-stabilized SeNPs (Ch-SeNPs) to identify new targets and pathways related to the antitumor mechanisms associated with Ch-SeNPs. The results obtained confirm the alteration of the cell cycle and the effect of Ch-SeNPs on different tumor suppressors and other molecules involved in key mechanisms related to cancer progression. Furthermore, we demonstrated the antioxidant properties of these nanoparticles and their capacity to induce senescence, which was further confirmed through the measurement of β-galactosidase activity.

Chitosan-Stabilized Selenium Nanoparticles and Metformin Synergistically Rescue Testicular Oxidative Damage and Steroidogenesis-Related Genes Dysregulation in High-Fat Diet/Streptozotocin-Induced Diabetic Rats.

Background: this study examined the metformin (MF) and/or chitosan stabilized selenium nanoparticles (CH-SeNPs) efficacy to alleviate the male reproductive function impairment in a high-fat diet feed with low-dose streptozotocin (HFD/STZ) induced type 2 diabetes mellitus (T2DM) diabetic rat model. Methods: control non-diabetic, HFD/STZ diabetic, HFD/STZ+MF, HFD/STZ+CH-SeNPs, and HFD/STZ+MF+CH-SeNPs rat groups were used. After 60 days, semen evaluation, hormonal assay, enzymatic antioxidant, lipid peroxidation, testis histopathology, and the steroidogenesis-related genes mRNA expressions were assessed. Results: in the HFD/STZ diabetic rats, sperm count and motility, male sexual hormones, and testicular antioxidant enzymes were significantly reduced. However, sperm abnormalities and testicular malondialdehyde were significantly incremented. The steroidogenesis-related genes, including steroidogenic acute regulatory protein (StAr), cytochrome11A1 (CYP11A1), cytochrome17A1 (CYP17A1), and hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), and the mitochondrial biogenesis related genes, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGCα) and sirtuin (SIRT), were significantly downregulated in the HFD/STZ diabetic rats. However, CYP19A1mRNA expression was significantly upregulated. In contrast, MF and/or CH-SeNPs oral dosing significantly rescued the T2DM-induced sperm abnormalities, reduced sperm motility, diminished sexual hormones level, testicular oxidative damage, and steroidogenesis-related genes dysregulation. In the MF and CH-SeNP co-treated group, many of the estimated parameters differ considerably from single MF or CH-SeNPs treated groups. Conclusions: the MF and CH-SeNPs combined treatment could efficiently limit the diabetic complications largely than monotherapeutic approach and they could be considered a hopeful treatment option in the T2DM.

Chitosan-stabilized selenium nanoparticles alleviate cardio-hepatic damage in type 2 diabetes mellitus model via regulation of caspase, Bax/Bcl-2, and Fas/FasL-pathway.

The present study was carried out to explore a novel strategy with the hypothesis that the combined treatment with standard antidiabetic drug metformin (MET) and chitosan stabilized nanoparticles (CTS-Se-NPs) may have a potential role on insulin level, hepatic damage and apoptosis, and cardiac injury markers of type 2 diabetes mellitus (T2DM) in rat model. T2DM was induced by a high fat diet (HFD) for 8weeks and a single injection of a low dose streptozotocin (STZ) (35mg/kg) in Sprague Dawley rats. A total number of one hundred rats were divided into five groups; the first served as a control (non-diabetic) group and the other four groups served as diabetic rats. The treatments were even mono or combined therapy by CTS-Se-NPs and/or MET for 8weeks. A group was given only MET (500mg/kg bw/day), another was administered only CTS-Se-NPs at a dose of 2mg se/kg/day, while the last group was given both of them (co-treated group). Biochemical, molecular and histopathological analyses were conducted to figure out the efficiency of the treatment by the monotherapeutic mode or combination therapy on the insulin level, oxidants/antioxidants status, inflammatory mediators, hepatic and cardiac injury biomarkers and apoptotic/anti-apoptotic gene expressions. Our results indicated that HFD/STZ-induced toxic effects on the serum, hepatic and cardiac tissues including a remarkable elevation of the oxidative and inflammatory mediators, and up-regulation of the apoptotic genes (Bax, Caspase-3, Fas, Fas-L) expression. Histologically, the heart tissue revealed various degenerative, vascular and inflammatory alterations characteristic to murine cardiomyopathy. Besides, livers from HFD-STZ-treated rats showed numerous cytotoxic, circulatory and inflammatory alterations. Combined therapy with MET and CTS-Se-NPs resulted in a better remarkable anti-diabetic effect demonstrated by substantial decreases in fasting blood glucose and insulin levels, and elevated with up-regulation of anti-apoptotic gene (BCL-2) and down-regulation of apoptotic genes after 8weeks of treatment than that revealed in the monotherapeutic strategy. In addition, it ameliorated the damage of cardiac and hepatic tissues and reduced lipid accumulation, and pro-inflammatory cytokines levels and restored the antioxidant capacity. It could be concluded that, the combined strategy applied in the current study have a potential role to limit the diabetic complications and restore insulin resistance to a higher extent than monotherapeutic strategy and could be considered a promising therapeutic alternative in T2DM rat model.

Chitosan-stabilized selenium nanoparticles attenuate acrylamide-induced brain injury in rats.

Acrylamide (ACR) is produced during food processing and has been shown to cause health problems. Selenium, especially in its nanoscale, is an important trace element in human nutrition. Chitosan-stabilized selenium nanoparticles (Ch-SeNPs) stability and its protective potential against ACR-induced injury in rats were evaluated. Ch-SeNPs displayed high radical-scavenging activity and reducing power that were not significantly changed for 60days at 4°C. The transmission electron microscopy images and dynamic light scattering results demonstrated high stability of Ch-SeNPs during storage. ACR (20mgkg-1 day-1 ) led to elevate the level of malondialdehyde, dopamine and noradrenaline in blood serum, and cerebral cortex. Ch-SeNPs (0.2mgkg-1 day-1 ) displayed more protection against ACR-induced damages comparing to Na2 SeO3 . More than 90% of the glutathione pool in the brain tissue was in reduced form. Correlation coefficient analysis demonstrated the attenuating effect of Ch-SeNPs against ACR-induced brain-injury and hormone imbalance. Administrating Ch-SeNPs 15days before ACR-treatment is required for obtaining the best protection. PRACTICAL APPLICATIONS: Ch-SeNPs used in the present study characterized by its high storage stability for two months without losing its antioxidant potential. After conducting toxicity tests, it is suggested to supplement some foods with Ch-SeNPs because of its high antioxidant potential and significant protection ability against the oxidative stress damages in living organisms. These advantages may nominate the Ch-SeNPs for several industrial applications in the field of food processing and protection.

Preparation and Characterization of Chitosan-Stabilized Selenium Nanoparticles for Ameliorating Experimentally Induced Diabetic Nephropathy in Rats

Chitosan-stabilized selenium nanoparticles (CTS-SeNPs) were prepared by reduction technique. Single phase structure of the SeNPs was confirmed using X-ray diffraction (XRD). Transmission Electron Microscope (TEM) showed that the particle size of the samples in the range of 15 nm. This experiment aimed to study the potential effect of (CTS-SeNPs) as a therapeutic factor in diabetic nephropathy in rats. Streptozotocin (STZ) was used to induce diabetes in rats; thirty-six numbers were divided into three groups; control, STZ-induced diabetic, and STZ-induced diabetic rats taken CTS-SeNPs groups at a dose (2 mg Se/kg/d). All groups were given respective treatment orally via gastric tube for 2 month. The obtained data showed that, the diabetic group revealed presence of Microalbuminurea, the indicator of diabetic nephropathy and showed a significant increase in fasting blood glucose, urea, creatinine, TAC and MDA, it is significant that high expression level of TGF-β1 and aldose reductase while the group treated with CTS-SeNPs revealed significant decline in all values compared to the diabetic group. Diabetic group showed a significant decrease in insulin level, GPx and SOD activity while, the treated group showed significant increase in these values compared to the diabetic group. Kidney tissue showed normal histological picture except for mild vascular and glomerular congestion in treated group when compared with diabetic one. Our experiment suggests that CTS-SeNPs can moderate diabetic nephropathy in streptozotocin-induced diabetic rats.

Physicochemical and functional properties of chitosan-stabilized selenium nanoparticles under different processing treatments.

Selenium nanoparticles (Se0NPs) have been well-characterized; however, whether processing affects their physicochemical and functional properties remains unknown. Here, chitosan (low and high molecular weight; CS(L) and CS(H), respectively) was used to stabilize Se0NPs, and the effects of heating (37℃, 70℃, and 95℃), freeze-drying-rehydration, and freeze-thawing on CS-Se0NPs physicochemical stability, Se release, antioxidant capacity, and antibacterial activity were evaluated. The results demonstrated that all treatments could cause CS-Se0NPs aggregation and Se release to varying degrees. Aggregation of CS-Se0NPs decreased their antibacterial activity, while Se release increased their antioxidant capacity with negligible effects on antibacterial activities. None of the CS-Se0NPs could tolerate freeze-thawing. CS(H)-Se0NPs exhibited better rehydration and heating stability than CS(L)-Se0NPs, although "rod-like" triclinic crystalline Se in CS(H)-Se0NPs, produced by 95℃ heating, decreased both antioxidant and antibacterial activities. Thus, these results provide a theoretical basis for the development and suitable application of CS-Se0NPs.

Antioxidant Capacity and Hepatoprotective Role of Chitosan-Stabilized Selenium Nanoparticles in Concanavalin A-Induced Liver Injury in Mice.

Selenium nanoparticles (SeNPs) have attracted wide attention for their use in nutritional supplements and nanomedicine applications. However, their potential to protect against autoimmune hepatitis has not been fully investigated, and the role of their antioxidant capacity in hepatoprotection is uncertain. In this study, chitosan-stabilized SeNPs (CS-SeNPs) were prepared by means of rapid ultra-filtration, and then their antioxidant ability and free-radical scavenging capacity were evaluated. The hepatoprotective potential of a spray-dried CS-SeNPs powder against autoimmune liver disease was also studied in the concanavalin A (Con A)-induced liver injury mouse model. CS-SeNPs with size of around 60 nm exhibited acceptable oxygen radical absorbance capacity and were able to scavenge DPPH, superoxide anion, and hydroxyl radicals. The CS-SeNPs powder alleviated Con A-caused hepatocyte necrosis and reduced the elevated levels of serum alanine transaminase, aspartate transaminase, and lactic dehydrogenase in Con A-treated mice. These results suggest that the CS-SeNPs powder protected the mice from Con-A-induced oxidative stress in the liver by retarding lipid oxidation and by boosting the activities of superoxide dismutase, glutathione peroxidase, and catalase, partly because of its ability to improve Se retention. In conclusion, SeNPs present potent hepatoprotective potential against Con A-induced liver damage by enhancing the redox state in the liver; therefore, they deserve further development.

Protective Effect of Selenium Nanoparticles against Acrylamide-Induced Hepatotoxicity in Albino Rats

Selenium nanoparticles have received wide attention due to their importance in nutrition compared to other forms of selenium used in food fortification. In the present study, chitosan-stabilized selenium nanoparticles (Ch-SeNPs) were prepared, characterized and evaluated for their hepatoprotective effect against acrylamide -induced hepatotoxicity in albino rats. According to TEM and Zetasizer analysis, the size of Ch-SeNPs produced in the present study were ranged from 18 to 55 nm with average of 22 nm. Acrylamide treatment led to elevation of the studied biochemical parameters of liver including total protein, albumin, globulin, alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase. Intake of Ch-SeNPs either 15 days prior to or simultaneously with the treatment with acrylamide led to enhance the biochemical parameters to be near the normal range. Same trend was obtained when rats were fed on sodium selenite, but Ch-SeNPs were more closely related to control group (untreated). The histopathological structure examination of rat liver emphasized the obtained biochemical results.The obtained results confirmed that, the intake of Ch-SeNPs 15 days before treatment by acrylamide had significant (< 0.05) protective effect against liver injury compared to the intake of these nanoparticles along with acrylamide.

Synthesis and antidiabetic properties of chitosan-stabilized selenium nanoparticles.

Chitosan-stabilized selenium nanoparticles (CTS-SeNPs) were prepared through the reduction of selenite acid with ascorbic acid. The optimal synthesis conditions of CTS-SeNPs were obtained by orthogonal experiments. Besides, the size, morphology and stability of CTS-SeNPs were characterized by transmission electron microscopy (TEM), scanning electron microscope (SEM) and dynamic light scattering (DLS). The results showed that, the CTS-SeNPs with diameter of about 54 nm could be obtained under the optimal conditions (temperature of 25 °C, reaction time of 2 h, Vc concentration of 0.04 M and the CTS concentration of 1.0 mg/mL). CTS-SeNPs were uniform spherical and could be stable for approximately 60 days at 4 °C. Further, the antidiabetic activities of CTS-SeNPs in streptozotocin (STZ)-induced diabetic mice were investigated as well. The results revealed that CTS-SeNPs at a dose of 2.0 mg Se/kg bw exhibited higher antidiabetic activity than other doses of CTS-SeNPs and other selenium compounds with the same selenium content.

Synergistic antifungal effect of chitosan-stabilized selenium nanoparticles synthesized by pulsed laser ablation in liquids against Candida albicans biofilms.

BackgroundCandida albicans is a major opportunistic fungal pathogen. One of the most important virulence factors that contribute to the pathogenesis of candidiasis is its ability to form biofilms. A key characteristic of Candida biofilms is their resistance to antifungal agents. Due to significant morbidity and mortality rates related to biofilm-associated drug resistance, there is an urgency to develop novel nanotechnology-based approaches preventing biofilm-related infections.MethodsIn this study, we report, for the first time, the synthesis of selenium nanoparticles by irradiating selenium pellets by nanosecond pulsed laser ablation in liquid chitosan as a capping agent. Synergy of the fungicidal effect of selenium nanoparticles and chitosan was quantified by the combination index theorem of Chou–Talalay.ResultsThis drug combination resulted in a potent fungicidal effect against a preformed C. albicans biofilm in a dose–response manner. By advanced electron microscopy techniques, we documented the adhesive and permeabilizing properties of chitosan, therefore allowing selenium nanoparticles to enter as the cell wall of the yeast became disrupted and distorted. Most importantly, we demonstrated a potent quantitative synergistic effect when compounds such as selenium and chitosan are combined.ConclusionThese chitosan-stabilized selenium nanoparticles could be used for ex vivo applications such as sterilizers for surfaces and biomedical devices.

Synthesis, characterization, and controlled release of selenium nanoparticles stabilized by chitosan of different molecular weights

Chitosan-stabilized selenium nanoparticles (SeNPs) have been reported, but there is no information on the effect of the chitosan molecular weight on the structure, stability, and selenium release properties of the SeNPs. Herein, we compared the uniform Se0 spherical nanoparticles prepared through the reduction of seleninic acid with ascorbic acid in the presence of chitosan with different molecular weights (Mws). We found that both low and high molecular weight chitosan-stabilized selenium nanoparticles exhibited core–shell microstructures with a size of about 103nm after 30 days growing through the “bottom–up approach” and “top–down approach,” respectively. Moreover, both chitosan SeNPs processed excellent stability towards pH and enzyme treatment. In contrast, selenium was easily released to different extents from these two chitosan SeNPs upon treatment with different free radicals. This makes these materials potentially useful as oral antioxidant supplements.

Effects of chitosan-stabilized selenium nanoparticles on cell proliferation, apoptosis and cell cycle pattern in HepG2 cells: Comparison with other selenospecies

Selenium is an essential element that plays an important role in many biological functions. Many studies have reported the potential beneficial effects of Se intake for cancer therapy and prevention, which are not only dose-dependent but also closely related to the properties of specific selenospecies. Selenium nanoparticles are considered a novel selenium compound with excellent antioxidant properties; however, little is known about the properties of selenium nanoparticles in comparison to other well-studied selenospecies. Here, we combined different independent bioanalytical approaches to carry out a comparison between the effects of selenium nanoparticles and other selenocompounds (inorganic and organic selenospecies) using an in-vitro model. The bioanalytical characterization of different parameters such as cell proliferation, apoptosis and cell cycle pattern on HepG2 cells has shown the unique properties of this relatively novel compound that support and complete prior evidences for future applications as chemotherapeutic agent.

Effect of Chitosan-Stabilized Selenium Nanoparticles on Cell Cycle Arrest and Invasiveness in Hepatocarcinoma Cells Revealed by Quantitative Proteomics

Selenium nanoparticles have been recently proposed as a potential chemotherapeutic agent due to its low toxicity and its ability to arrest the cell cycle of cancer cells. However, the biochemical mechanisms associated to this effect have not yet been uncovered. We evaluate here the potential of chitosan-stabilized selenium nanoparticles to induce cell cycle arrest and to inhibit in-vitro invasiveness in HepG2 cells. In addition, we use a quantitative proteomic approach to identify potential protein targets involved in the mechanisms associated to selenium nanoparticles exposure. Our data suggest that the induction of the cell cycle arrest at the S phase is mediated by de-regulation of the eIF3 protein complex. We found additional de-regulated proteins upon selenium nanoparticles exposure that could also be involved in the overall inhibition of cell proliferation. These findings not only support the potential of chitosan-stabilized selenium nanoparticles as anti-cancer therapy but also provide a deeper insight into the mechanisms associated to their chemotherapeutic effects.