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Exogenous antioxidant materials mimicking endogenous antioxidant systems are commonly used for the treatment of oxidative stress-induced injuries. Thus, artificial enzymes have emerged as promising candidates for balancing and treating the dysregulation of redox homeostasis in vivo. Herein, a one-pot hydrothermal strategy for the facile preparation of MoSe2-polyvinylpyrrolidone (PVP) nanoparticles (NPs) is reported. The synthesized NPs were biodegradable due to their exposure to oxygen and exhibited high stability. Moreover, they effectively mimicked various naturally occurring enzymes (including catalase, superoxide dismutase, peroxidase, and glutathione peroxidase) and scavenged free radicals, such as 3-ethylbenzothiazoline-6-sulfonic acid, ·OH, ·O2−, and 1,1-diphenyl-2-picrylhydrazyl radical. Further apoptosis detection studies revealed that MoSe2-PVP NPs significantly increased the cell survival probability in H2O2 in a concentration-dependent manner. The cytoprotective effect of MoSe2-PVP NPs was explored for an animal model of acute pancreatitis, which confirmed its remarkable therapeutic efficacy. Owing to the biodegradable and biocompatible nature of MoSe2-PVP NPs, the findings of this work can stimulate the development of other artificial nanoenzymes for antioxidant therapies. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer worldwide and still lacks effective therapy. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. However, whether ivermectin affects CRC is still unclear. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. We used CCK-8 assay to determine the cell viability, used an optical microscope to measure cell morphology, used Annexin V-FITC/7-AAD kit to determine cell apoptosis, used Caspase 3/7 Activity Apoptosis Assay Kit to evaluate Caspase 3/7 activity, used Western blot to determine apoptosis-associated protein expression, and used flow cytometry and fluorescence microscope to determine the reactive oxygen species (ROS) levels and cell cycle. The results demonstrated that ivermectin dose-dependently inhibited colorectal cancer SW480 and SW1116 cell growth, followed by promoting cell apoptosis and increasing Caspase-3/7 activity. Besides, ivermectin upregulated the expression of proapoptotic proteins Bax and cleaved PARP and downregulated antiapoptotic protein Bcl-2. Mechanism analysis showed that ivermectin promoted both total and mitochondrial ROS production in a dose-dependent manner, which could be eliminated by administering N-acetyl-l-cysteine (NAC) in CRC cells. Following NAC treatment, the inhibition of cell growth induced by ivermectin was reversed. Finally, ivermectin at low doses (2.5 and 5 µM) induced CRC cell arrest. Overall, ivermectin suppressed cell proliferation by promoting ROS-mediated mitochondrial apoptosis pathway and inducing S phase arrest in CRC cells, suggesting that ivermectin might be a new potential anticancer drug therapy for human colorectal cancer and other cancers. [ABSTRACT FROM AUTHOR]

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted attention due to its enhanced tumor therapy effect. This study proposes a novel nanoenzyme-based theranostic nanoplatform, IrO2@MSN@PDA-BSA(Ce6), for the combined PTT and PDT of tumors. IrO2 was prepared by a simple hydrolysis method and coated with a thin layer of mesoporous silica (MSN) to facilitate the physical adsorption of Chlorin e6 (Ce6). The PDA coating and IrO2 NPs of the nanoplatform demonstrated an improved photothermal conversion efficiency of 29.8% under NIR irradiation. Further, the Ce6 loading imparts materials with the ability to produce reactive oxygen species (ROS) under 660 nm NIR laser irradiation. It was also proved that the IrO2 NPs could catalyze the hydrogen peroxide (H2O2) in the tumor microenvironment (TME) to generate endogenous oxygen (O2), thereby enhancing the efficiency of PDT. The in vitro and in vivo experiments indicated that the nanocomposite was highly biocompatible and could produce a satisfactory tumor therapeutic effect. Thus, the findings of the present study demonstrate the viability of using theranostic nanoenzymes for translational medicine. [ABSTRACT FROM AUTHOR]

[Display omitted] • Efficient synthesis of MoSe 2 @PVP NSs via a simple one-pot synthesis. • MoSe 2 @PVP NSs have high physiological stability, biosafety and metabolizability. • MoSe 2 @PVP NSs can mimic the antioxidant properties of CAT, SOD, POD, and GPx. • MoSe 2 @PVP NSs eliminate many ROS and RNS and demonstrate a thermal durability. • MoSe 2 @PVP NSs exhibite high anti-inflammatory efficacy in the AP mouse model. Acute pancreatitis (AP) is a disease with high mortality which could cause an inflammatory responses such as edema and necrosis of the pancreatic tissue. Studies have proved that the excessive produced reactive oxygen species (ROS) and reactive nitrogen species (RNS) play an important role in the pathogenesis of AP. Although progresses have been made for ROS and RNS elimination using artificial enzymes, biocompatible nanomaterials with advanced multi-enzymatic activities have been rarely studied. In this study, we constructed a simple and efficient method to fabricate a two-dimensional (2D) MoSe 2 @PVP nanosheets (NSs) as an artificial enzyme to treat oxidative stress-related diseases. Both in vitro and in vivo experiments proved that MoSe 2 @PVP NSs have good biocompatibility. Interestingly, the MoSe 2 @PVP NSs simultaneously showed the thermal durable peroxidase, catalase, superoxide dismutase, and glutathione peroxidase mimicking capacities, which endowed the material with good ROS and RNS scavenging abilities. The MoSe 2 @PVP NSs were engaged in treating the AP in an animal model, which led to a significant down-regulation of serum levels of amylase, IL-6, IL-1β, and TNF-α. Further H&E staining of pancreatic tissue validated the AP therapeutic effect of MoSe 2 @PVP NSs. We hope that our research will facilitate the development of multifunctional artificial enzymes for the treating of oxidative stress-related diseases. [ABSTRACT FROM AUTHOR]