Black phosphorus (BP), as an emerging successor to layered two-dimensional materials, has attracted extensive interest in cancer therapy. Toxicological studies on BP are of great importance for potential biomedical applications, yet not systemically explored. Herein, toxicity and oxidative stress of BP quantum dots (BPQDs) at cellular, tissue, and whole-body levels are evaluated by performing the systemic in vivo and in vitro experiments. In vitro investigations show that BPQDs at high concentration (200 μg/mL) exhibit significant apoptotic effects on HeLa cells. In vivo investigations indicate that oxidative stress, including lipid peroxidation, reduction of catalase activity, DNA breaks, and bone marrow nucleated cells (BMNC) damage, can be induced by BPQDs transiently but recovered gradually to healthy levels. No apparent pathological damages are observed in all organs, especially in the spleen and kidneys, during the 30-day period. This work clearly shows that BPQDs can cause acute toxicities by oxidative stress responses, but the inflammatory reactions can be recovered gradually with time for up to 30 days. Thus, BPQDs do not give rise to long-term appreciable toxicological responses.

Metal nanozyme has attracted wide interest for biomedicine, and a highly catalytic material in the physiological environment is highly desired. However, catalytic selectivity of nanozyme is still highly challenging, limiting its wide application. Here, we show a trimetallic (triM) nanozyme with highly catalytic activity and environmental selectivity. Enzyme-mimicked investigations find that the triM system possesses multi-enzyme-mimetic activity for removing reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as 1O2, H2O2, •OH, and •NO. Importantly, triM nanozyme exhibits the significant neutral environment preference for removing the •OH, 1O2, and •NO free radical, indicating its highly catalytic selectivity. The density functional theory (DFT) calculations reveal that triM nanozyme can capture electrons very easily and provides more attraction to reactive oxygen and nitrogen species (RONS) radicals in the neutral environment. In vitro experiments show that triM nanozyme can improve the viability of injured neural cell. In the LPS-induced brain injury model, the superoxide dismutase (SOD) activity and lipid peroxidation can be greatly recovered after triM nanozyme treatment. Moreover, the triM nanozyme treatment can significantly improve the survival rate, neuroinflammation, and reference memory of injured mice. Present work provides a feasible route for improving selectivity of nanozyme in the physiological environment as well as exploring potential applications in brain science.

Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)–dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.

Catalytic nanomaterials can be used extrinsically to combat diseases associated with a surplus of reactive oxygen species (ROS). Rational design of surface morphologies and appropriate doping can substantially improve the catalytic performances. In this work, a class of hollow polyvinyl pyrrolidone-protected PtPdRh nanocubes with enhanced catalytic activities for in vivo free radical scavenging is proposed. Compared with Pt and PtPd counterparts, ternary PtPdRh nanocubes show remarkable catalytic properties of decomposing H O via enhanced oxygen reduction reactions. Density functional theory calculation indicates that the bond of superoxide anions breaks for the energetically favorable status of oxygen atoms on the surface of PtPdRh. Viability of cells and survival rate of animal models under exposure of high-energy γ radiation are considerably enhanced by 94% and 50% respectively after treatment of PtPdRh nanocubes. The mechanistic investigations on superoxide dismutase (SOD) activity, malondialdehyde amount, and DNA damage repair demonstrate that hollow PtPdRh nanocubes act as catalase, peroxidase, and SOD analogs to efficiently scavenge ROS.

Two-dimensional WS 2 materials have attracted wide attention in condensed physics and materials science due to its unique geometric and electronic structures. Particularly, WS 2 shows extraordinary catalytic activities when its size decreases to ultrasmall, which provides potential opportunities for medical applications. In this work, WS 2 quantum dots with strong catalytic properties were used for in vitro and in vivo protection from ionizing radiation induced cell damages. WS 2 quantum dots possess unique optical properties of blue photoluminescence emission and excitation-wavelength dependent emission profiles. In vitro studies showed that cell viability can be considerably improved and cellular reactive oxygen species (ROS) can be removed by WS 2 quantum dots. In vivo studies showed WS 2 quantum dots can effectively protect the hematopoietic system and DNA from damages caused by high-energy radiation through removing whole-body excessive ROS. Furthermore, WS 2 quantum dots showed nearly 80% renal clearance within 24 h post injection and did not cause any obvious toxicities in up to 30 days after treatment.