Self-cascade MoS2 nanozymes for efficient intracellular antioxidation and hepatic fibrosis therapy.

Cascade biocatalytic reactions involving multiple antioxidative enzymes are necessary in living cells to regulate cellular metabolism and redox homeostasis. Substantial efforts have been made to construct cascade reactions through engineered enzyme mimics to improve intracellular metabolic flux, especially under pathophysiological conditions. Here, we show that MoS2 nanozymes exhibit activities of four major cellular cascade antioxidant enzymes, including superoxide dismutase, catalase, peroxidase, and glutathione peroxidase. Meanwhile, MoS2 nanozymes attenuate electron transfer in cytochrome c/H2O2 to ameliorate the inherent antioxidant defense system under stress conditions. Thus, MoS2 nanozymes function as a self-cascade platform to inhibit intracellular reactive oxygen species (ROS) production by modulating mitochondrial function and scavenging abundant ROS through their intrinsic antioxidant capacity. Density functional theory calculations reveal the underlying mechanisms of the intracellular environment-dependent catalase-like activity of MoS2 nanozymes. Furthermore, we find that the MoS2 nanozymes play a cytoprotective role in cells and significantly improve the treatment outcomes in a hepatic fibrosis mouse model. These results demonstrate the ROS-scavenging capacity of a single-component MoS2 nanozyme-based cascade reaction system and reveal the in-depth mechanism, which may advance the development of nanozyme-based antioxidative agents.