Jiangxi University of Traditional Chinese Medicine

The rapid development of modern industry and excessive consumption of petroleum-based polymers have triggered a double crisis presenting a shortage of nonrenewable resources and environmental pollution. However, this has provided an opportunity to stimulate researchers to harness native biobased materials for novel advanced materials and applications. Nanocellulose-based aerogels, using abundant and sustainable cellulose as raw material, present a third-generation of aerogels that combine traditional aerogels with high porosity and large specific surface area, as well as the excellent properties of cellulose itself. Currently, nanocellulose aerogels provide a highly attention-catching platform for a wide range of functional applications in various fields, e.g., adsorption, separation, energy storage, thermal insulation, electromagnetic interference shielding, and biomedical applications. Here, the preparation methods, modification strategies, composite fabrications, and further applications of nanocellulose aerogels are summarized, with additional discussions regarding the prospects and potential challenges in future development.

OBJECTIVE: To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN: Network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES: Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS: 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS: In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153180.

Natural products have been an invaluable and useful source of anticancer agents over the years. Several compounds have been synthesized from natural products by modifying their structures or by using naturally occurring compounds as building blocks in the synthesis of these compounds for various purposes in different fields, such as biology, medicine, and engineering. Multiple modern and costly treatments have been applied to combat cancer and limit its lethality, but the results are not significantly refreshing. Natural products, which are a significant source of new therapeutic drugs, are currently being investigated as potential cytotoxic agents and have shown a positive trend in preclinical research and have prompted numerous innovative strategies in order to combat cancer and expedite the clinical research. Natural products are becoming increasingly important for drug discovery due to their high molecular diversity and novel biofunctionality. Furthermore, natural products can provide superior efficacy and safety due to their unique molecular properties. The objective of the current review is to provide an overview of the emergence of natural products for the treatment and prevention of cancer, such as chemosensitizers, immunotherapeutics, combinatorial therapies with other anticancer drugs, novel formulations of natural products, and the molecular mechanisms underlying their anticancer properties.

coordinative bonds are highly porous, crystalline materials. Their tunable porosity, chemical composition, size and shape, and easy surface functionalization make this large family more and more popular for drug delivery. There is a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications. This article presents an overall review and perspectives of MOFs-based drug delivery systems (DDSs), starting with the MOFs classification adapted for DDSs based on the types of constituting metals and ligands. Then, the synthesis and characterization of MOFs for DDSs are developed, followed by the drug loading strategies, applications, biopharmaceutics and quality control. Importantly, a variety of representative applications of MOFs are detailed from a point of view of applications in pharmaceutics, diseases therapy and advanced DDSs. In particular, the biopharmaceutics and quality control of MOFs-based DDSs are summarized with critical issues to be addressed. Finally, challenges in MOFs development for DDSs are discussed, such as biostability, biosafety, biopharmaceutics and nomenclature.

Abstract The separation of C 2 H 2 /CO 2 is not only industrially important for acetylene purification but also scientifically challenging owing to their high similarities in physical properties and molecular sizes. Ultramicroporous metal-organic frameworks (MOFs) can exhibit a pore confinement effect to differentiate gas molecules of similar size. Herein, we report the fine-tuning of pore sizes in sub-nanometer scale on a series of isoreticular MOFs that can realize highly efficient C 2 H 2 /CO 2 separation. The subtle structural differences lead to remarkable adsorption performances enhancement. Among four MOF analogs, by integrating appropriate pore size and specific binding sites, [Cu(dps) 2 (SiF 6 )] (SIFSIX-dps-Cu, SIFSIX = SiF 6 2- , dps = 4.4’-dipyridylsulfide, also termed as NCU-100) exhibits the highest C 2 H 2 uptake capacity and C 2 H 2 /CO 2 selectivity. At room temperature, the pore space of SIFSIX-dps-Cu significantly inhibits CO 2 molecules but takes up a large amount of C 2 H 2 (4.57 mmol g −1 ), resulting in a high IAST selectivity of 1787 for C 2 H 2 /CO 2 separation. The multiple host-guest interactions for C 2 H 2 in both inter- and intralayer cavities are further revealed by dispersion-corrected density functional theory and grand canonical Monte Carlo simulations. Dynamic breakthrough experiments show a clean C 2 H 2 /CO 2 separation with a high C 2 H 2 working capacity of 2.48 mmol g −1 .

MXenes, as a novel kind of two-dimensional (2D) materials, were first discovered by Gogotsi et al. in 2011. Owing to their multifarious chemical compositions and outstanding physicochemical properties, the novel types of 2D materials have attracted intensive research interest for potential applications in various fields such as energy storage and conversion, environmental remediation, catalysis, and biomedicine. Although many achievements have been made in recent years, there still remains a lack of reviews to summarize these recent advances of MXenes, especially in biomedical fields. Understanding the current status of surface modification, biomedical applications and toxicity of MXenes and related materials will give some inspiration to the development of novel methods for the preparation of multifunctional MXene-based materials and promote the practical biomedical applications of MXenes and related materials. In this review, we present the recent developments in the surface modification of MXenes and the biomedical applications of MXene-based materials. In the first section, some typical surface modification strategies were introduced and the related issues were also discussed. Then, the potential biomedical applications (such as biosensor, biological imaging, photothermal therapy, drug delivery, theranostic nanoplatforms, and antibacterial agents) of MXenes and related materials were summarized and highlighted in the following sections. In the last section, the toxicity and biocompatibility of MXenes in vitro were mentioned. Finally, the development, future directions and challenges about the surface modification of MXene-based materials for biomedical applications were discussed. We believe that this review article will attract great interest from the scientists in materials, chemistry, biomedicine and related fields and promote the development of MXenes and related materials for biomedical applications.

High Resolution Image Download MS PowerPoint Slide Pneumonia, such as acute lung injury (ALI), has been a type of lethal disease that is generally caused by uncontrolled inflammatory response and excessive generation of reactive oxygen species (ROS). Herein, we report Fe-curcumin-based nanoparticles (Fe-Cur NPs) with nanozyme functionalities in guiding the intracellular ROS scavenging and meanwhile exhibiting anti-inflammation efficacy for curing ALI. The nanoparticles are noncytotoxic when directing these biological activities. Mechanism studies for the anti-inflammation aspects of Fe-Cur NPs were systematically carried out, in which the infected cells and tissues were alleviated through downregulating levels of several important inflammatory cytokines (such as TNF-α, IL-1β, and IL-6), decreasing the intracellular Ca 2+ release, inhibiting NLRP3 inflammasomes, and suppressing NF-κB signaling pathways. In addition, we performed both the intratracheal and intravenous injection of Fe-Cur NPs in mice experiencing ALI and, importantly, found that the accumulation of such nanozymes was enhanced in lung tissue (better than free curcumin drugs), demonstrating its promising therapeutic efficiency in two different administration methods. We showed that the inflammation reduction of Fe-Cur NPs was effective in animal experiments and that ROS scavenging was also effectively achieved in lung tissue. Finally, we revealed that Fe-Cur NPs can decrease the level of macrophage cells (CD11b lo F4/80 hi ) and CD3 + CD45 + T cells in mice, which could help suppress the inflammation cytokine storm caused by ALI. Overall, this work has developed the strategy of using Fe-Cur NPs as nanozymes to scavenge intracellular ROS and as an anti-inflammation nanodrugs to synergistically cure ALI, which may serve as a promising therapeutic agent in the clinical treatment of this deadly disease. Fe-Cur NP nanozymes were designed to attenuate ALI by clearing intracellular ROS and alleviating inflammation synergistically. Relevant cytokines, inflammasomes, and signaling pathways were studied.

Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer that is difficult to treat due to its resistance to both radiation and chemotherapy. This resistance is largely due to the unique biology of GBM cells, which can evade the effects of conventional treatments through mechanisms such as increased resistance to cell death and rapid regeneration of cancerous cells. Additionally, the blood-brain barrier makes it difficult for chemotherapy drugs to reach GBM cells, leading to reduced effectiveness. Despite these challenges, there are several treatment options available for GBM. The standard of care for newly diagnosed GBM patients involves surgical resection followed by concurrent chemoradiotherapy and adjuvant chemotherapy. Emerging treatments include immunotherapy, such as checkpoint inhibitors, and targeted therapies, such as bevacizumab, that attempt to attack specific vulnerabilities in GBM cells. Another promising approach is the use of tumor-treating fields, a type of electric field therapy that has been shown to slow the growth of GBM cells. Clinical trials are ongoing to evaluate the safety and efficacy of these and other innovative treatments for GBM, intending to improve with outcomes for patients.

Pyroptosis, a type of programmed cell death (PCD), is characterized by cell swelling with bubbles, and the release of inflammatory cell cytokines. Cucurbitacin B (CuB), extracted from muskmelon pedicel, is a natural bioactive product that could effectively exert anti-tumor activities in lung cancer. However, the exact molecular mechanisms and the direct targets of CuB in non-small cell lung cancer (NSCLC) remain to be discovered. Here, we firstly found that CuB exerted an anti-tumor effect via pyroptosis in NSCLC cells and NSCLC mice models. Next, based on the molecular docking and cellular thermal shift assay (CETSA), we identified that CuB directly bound to Toll-like receptor 4 (TLR4) to activate the NLRP3 inflammasome, which further caused the separation of N- and C-terminals of Gasdermin D (GSDMD) to execute pyroptosis. Moreover, CuB enhanced the mitochondrial reactive oxygen species (ROS), mitochondrial membrane protein Tom20 accumulation, and cytosolic calcium (Ca2+) release, leading to pyroptosis in NSCLC cells. Silencing of TLR4 inhibited CuB-induced pyroptosis and decreased the level of ROS and Ca2+ in A549 cells. In vivo study showed that CuB treatment suppressed lung tumor growth in mice via pyroptosis without dose-dependent manner, and CuB at 0.75 mg/kg had a better anti-tumor effect compared to the Gefitinib group. Taken together, our findings revealed the mechanisms and targets of CuB triggering pyroptosis in NSCLC, thus supporting the notion of developing CuB as a promising therapeutic agent for NSCLC.

Abstract The challenge of bacterial infection increases the risk of mortality and morbidity in acute and chronic wound healing. Silver nanoparticles (Ag NPs) are a promising new version of conventional antibacterial nanosystem to fight against the bacterial resistance in concern of the drug discovery void. However, there are several challenges in controlling the size and colloidal stability of Ag NPs, which readily aggregate or coalesce in both solid and aqueous state. In this study, a template‐guided synthesis of ultrafine Ag NPs of around 2 nm using water‐soluble and biocompatible γ‐cyclodextrin metal‐organic frameworks (CD‐MOFs) is reported. The CD‐MOF based synthetic strategy integrates AgNO 3 reduction and Ag NPs immobilization in one pot achieving dual functions of reduced particle size and enhanced stability. Meanwhile, the synthesized Ag NPs are easily dispersible in aqueous media and exhibit effective bacterial inhibition. The surface modification of cross‐linked CD‐MOF particles with GRGDS peptide boosts the hemostatic effect that further enhances wound healing in synergy with the antibacterial effect. Hence, the strategy of ultrafine Ag NPs synthesis and immobilization in CD‐MOFs together with GRGDS modification holds promising potential for the rational design of effective wound healing devices.

OBJECTIVE: The purpose of this study was to evaluate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on cardiovascular disease (CVD) risk factors in adults with overweight and obesity. METHODS: Twenty-two articles were included by searching six databases, the total number of subjects was 620 in these articles. Outcomes were synthesised using a random-effects meta-analysis of the Standardized mean difference (SMD) in CVD risk factors. RESULTS: HIIT and MICT resulted in statistically significant reductions in Weight, BMI, fat%, total cholesterol(TC), and improvement in VO2max. Compared with MICT, subgroup of durations of HIIT training interval ≥2 min can significantly increase VO2max (SMD = 0.444, 95% CI:0.037~0.851,P = 0.032), subgroup of energy expenditure of HIIT equal to MICT can significantly increase VO2max (SMD = 0.399, 95% CI:0.106~0.692,P = 0.008). CONCLUSIONS: HIIT appears to provide similar benefits to MICT for improving body composition, VO2maxand TC, but HIIT spent less time than MICT by 9.7 min on one session. HIIT is superior to MICT in improving cardiopulmonary fitness when durations of HIIT training interval ≥2 min or energy expenditure of HIIT same as MICT. PROSPERO ID: CRD42016045835.

The initiation and development of major inflammatory diseases, i.e., cancer, vascular inflammation, and some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these diseases, whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo, poor penetration across biological barriers, and rapid clearance by the reticuloendothelial system. Drug delivery strategies are potent to promote their delivery. Herein, we reviewed the potential targets for immunotherapy against the major inflammatory diseases, discussed the biologics and drug delivery systems involved in the immunotherapy, particularly highlighted the approved therapy tactics, and finally offer perspectives in this field.

Exopolysaccharide (EPS) was extracted and purified from Lactobacillus plantarum WLPL04, which has been confirmed previously as a potential probiotic for its antagonistic and immune-modulating activity. It has a molecular weight of 6.61 × 10 4 Da, consisting of xylose, glucose, and galactose in an approximate molar ratio of 3.4:1.8:1. Microstructural studies demonstrated that the EPS appeared as a smooth sheet structure with many homogeneous rod-shaped lumps. The preliminary in vitro assays indicated that the EPS could significantly inhibit the adhesion of Escherichia coli O157:H7 to HT-29 cells in competition, replacement, and inhibition assays at a dose of 1.0 mg/mL, with an inhibition rate of 20.24 ± 2.23, 29.71 ± 1.21, and 30.57 ± 1.73%, respectively. Additionally, the EPS exhibited strong inhibition against biofilm formation by pathogenic bacteria, including Pseudomonas aeruginosa CMCC10104, E. coli O157:H7, Salmonella Typhimurium ATCC13311, and Staphylococcus aureus CMCC26003. Furthermore, the EPS showed good inhibitory activity against the proliferation of HT-29 cells. The characteristics and bioactivities of this EPS may make it a promising candidate in developing functional food.

Flavonoids are well known for their extensive health benefits. However, few studies compared the differences between flavonoid O-glycoside and C-glycoside. In this work, flavonoid O-glycoside (isoquercitrin), C-glycoside (orientin), and their aglycones (quercetin and luteolin) were chosen to compare their differences on antioxidant activities and metabolism during in vitro digestion and in vivo. In vitro digestion, the initial antioxidant activity of the two aglycones was very high; however, they both decreased more sharply than their glycosides in the intestinal phase. The glycosidic bond of flavonoid O-glycoside was broken in the gastric and intestinal stage, while the C-glycoside remained unchanged. In vivo, flavonoid O-glycoside in plasma was more elevated than C-glycoside on the antioxidant activity; however, flavonoid C-glycoside in urine was higher than O-glycoside. These results indicate that differences of flavonoid glycosides and their aglycones on antioxidant activity are closely related to their structural characteristics and metabolism in different samples. Aglycones possessed higher activity but unstable structures. On the contrary, the sugar substituents reduced the activity of flavonoids while improving their stability and helping to maintain antioxidant activities after digestion. Especially the C-glycoside was more stable because the stability of the C-C bond is higher than that of the C-O bond, which contributes to the difference between flavonoid O-glycoside and C-glycoside on the absorption and metabolism in vivo. This study provided a new perspective for comparing flavonoid O-glycoside, flavonoid C-glycoside, and their aglycones on their structure-activity relationship and metabolism.

AIM: To assess the effects of sodium-glucoseco-transporter-2 (SGLT2) inhibitors on diabetic ketoacidosis (DKA) in patients with type 2 diabetes. MATERIALS AND METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception to 13 June 2019 for randomized controlled trials (RCTs) that compared SGLT2 inhibitors with control in patients with type 2 diabetes. Paired reviewers independently screened citations, assessed the risk of bias and extracted data. Peto's method was used as the primary approach to pool the effect of SGLT2 inhibitors on DKA. Sensitivity analyses with the alternative effect measure (risk ratio) or pooling method (Mantel-Haenszel), the use of continuity correction of 0.5 for zero-event trials or a generalized linear mixed model were conducted. Six preplanned subgroup analyses were performed to explore heterogeneity. The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence. RESULTS: = 8%; RD 1.7 more events, 95% CI 0.6 more to 3.4 more events per 1000 over 5 years; high-quality evidence). Sensitivity analyses showed similar results. The subgroup analyses by mean age (interaction P = 0 .02) and length of follow-up (interaction P = 0 .03) showed a larger relative effect among older patients (aged ≥60 years) and those with longer use of SGLT2 inhibitors (>52 weeks). CONCLUSIONS: High-quality evidence suggests that SGLT2 inhibitors may increase the risk of DKA in patients with type 2 diabetes. The apparent differences in treatment effects among patients of a different age or follow-up were probable, suggesting the advisability of caution in patients with long-term use of SGLT2 inhibitors or in older patients.

Combination chemotherapy is a common practice in clinical management of malignancy. Synergistic therapeutic outcome is only achieved when tumor cells are exposed to cells in an optimal ratio. However, due to diverse physicochemical properties of drugs, no free drug cocktails or nanomaterials are capable of co‐loading and co‐delivering drugs at an optimal ratio. Herein, we develop a novel nano‐platform with precise ratiometric co‐loading and co‐delivery of two hydrophilic drugs for synergistic anti‐tumor effects. Based on previous work, we utilize a solvent displacement method to ratiometrically load dioleoyl phosphatidic acid (DOPA)‐gemcitabine monophosphate (GMP) and DOPA coated cisplatin‐precipitate nanocores into the same PLGA NP. These cores are designed to have similar hydrophobic surface properties. GMP and cisplatin are engineered into PLGA NP at an optimal synergistic ratio (5:1, mol:mol) with over 70% encapsulation efficiency and were ratiometrically taken up by tumor cells in vitro and in vivo. These PLGA NP exhibit synergistic anti‐cancer effects in a stroma‐rich bladder tumor model. A single injection of dual drugs in PLGA NP can significantly inhibit tumor growth. This nanomaterial‐system solves problems related to ratiometric co‐loading and co‐delivery of different hydrophilic moieties and provides possibilities for co‐loading hydrophilic drugs with hydrophobic drugs for combination therapy.

Mixed-lineage kinase domain-like protein (MLKL) is essential for TNF-α-induced necroptosis. How MLKL promotes cell death is still under debate. Here we report that MLKL forms SDS-resistant, disulfide bond-dependent polymers during necroptosis in both human and mouse cells. MLKL polymers are independent of receptor-interacting protein kinase 1 and 3 (RIPK1/RIPK3) fibers. Large MLKL polymers are more than 2 million Da and are resistant to proteinase K digestion. MLKL polymers are fibers 5 nm in diameter under electron microscopy. Furthermore, the recombinant N-terminal domain of MLKL forms amyloid-like fibers and binds Congo red dye. MLKL mutants that cannot form polymers also fail to induce necroptosis efficiently. Finally, the compound necrosulfonamide conjugates cysteine 86 of human MLKL and blocks MLKL polymer formation and subsequent cell death. These results demonstrate that disulfide bond-dependent, amyloid-like MLKL polymers are necessary and sufficient to induce necroptosis.

Excessive oxidative stress in cancer cells can induce cancer cell death. Anticancer activity and drug resistance of chemotherapy are closely related to the redox state of tumor cells. Herein, five lipophilic Pt(IV) prodrugs were synthesized on the basis of the most widely used anticancer drug cisplatin, whose anticancer efficacy and drug resistance are closely related to the intracellular redox state. Subsequently, a series of cisplatin-sensitive and drug-resistant cell lines as well as three patient-derived primary ovarian cancer cells have been selected to screen those prodrugs. To verify if the disruption of redox balance can be combined with these Pt(IV) prodrugs, we then synthesized a polymer with a diselenium bond in the main chain for encapsulating the most effective prodrug to form nanoparticles (NP(Se)s). NP(Se)s can efficiently break the redox balance via simultaneously depleting GSH and augmenting ROS, thereby achieving a synergistic effect with cisplatin. In addition, genome-wide analysis via RNA-seq was employed to provide a comprehensive understanding of the changes in transcriptome and the alterations in redox-related pathways in cells treated with NP(Se)s and cisplatin. Thereafter, patient-derived xenograft models of hepatic carcinoma (PDX HCC ) and multidrug-resistant lung cancer (PDX MDR ) were established to evaluate the therapeutic effect of NP(Se)s, and a significant antitumor effect was achieved on both models with NP(Se)s. Overall, this study provides a promising strategy to break the redox balance for maximizing the efficacy of platinum-based cancer therapy.

Product 1 (82.25% valencene), product 2 (73.36% decanal), product 3 (78.12% octanal), and product 4 (90.61% linalool) were isolated from sweet orange oil by combined usage of molecular distillation and column chromatography. The antioxidant activity of sweet orange oil and these products was investigated using 2,2-diphenyl-1-picrylhydrazyl and reducing power assays. In this test, product 1 (82.25% valencene), product 2 (73.36% decanal), and product 4 (90.61% linalool) had antioxidant activity, but lower than sweet orange oil. The antimicrobial activity was investigated in order to evaluate their efficacy against 5 microorganisms. The results showed that sweet orange oil, product 2 (73.36% decanal), product 3 (78.12% octanal), and product 4 (90.61% linalool) had inhibitory and bactericidal effect on the test microorganisms (except Penicillium citrinum). Valencene did not show any inhibitory effect. Saccharomyces cerivisiae was more susceptible, especially to the crude sweet orange oil (minimal inhibitory concentration 6.25 μL/mL). The cytotoxicity was evaluated on Hela cells using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. All test samples showed significant cytotoxicity on the cell lines with IC(50) values much less than 20 μg/mL.

Nano silver is one of the most widely used engineering nanomaterials with antimicrobial activity against bacteria, fungi, and viruses. However, the widespread application of nano silver preparations in daily life raises concerns about public health. Although several review articles have described the toxicity of nano silver to specific major organs, an updated comprehensive review that clearly and systematically outlines the harmful effects of nano silver is lacking. This review begins with the routes of exposure to nano silver and its distribution in vivo. The toxic reactions are then discussed on three levels, from the organ to the cellular and subcellular levels. This review also provides new insights on adjusting the toxicity of nano silver by changing their size and surface functionalization and their combination with other materials to form a composite formulation. Finally, future development, challenges, and research directions are discussed.