Self‐Propelled Ultrasmall AuNPs‐Tannic Acid Hybrid Nanozyme with ROS‐Scavenging and Anti‐Inflammatory Activity for Drug‐Induced Liver Injury Alleviation

Abstract Developing nanomedicines with superior reactive oxygen species (ROS) scavenging capability has emerged as a promising strategy in treating ROS‐related diseases, for example, drug‐induced liver injury. However, designing nanoscavengers with the self‐propelling ability to scavenge ROS actively remains challenging. Here, a self‐propelled silica‐supported ultrasmall gold nanoparticles‐tannic acid hybrid nanozyme (SAuPTB) is designed that can effectively alleviate acetaminophen (APAP)‐induced liver injury by scavenging excessive ROS and regulating inflammation. SAuPTB exhibits multienzyme activity and displays significantly enhanced diffusion under hydrogen peroxide (H 2 O 2 ). This in vitro research shows that SAuPTB can effectively eliminate ROS, increasing the viability of H 2 O 2 ‐stimulated cells and reducing the cytotoxicity of APAP/H 2 O 2 ‐treated AML12 cells. The in vivo studies show that SAuPTB can accumulate at inflammatory sites in mouse liver, resulting in the decrease of alanine aminotransferase, aspartate aminotransferase, and ROS, reduction in pro‐inflammatory cytokines and chemokines, hence reduced hepatocyte necrosis, liver injury, and mortality. Furthermore, SAuPTB activates the nuclear erythroid 2‐related factor 2 pathway to upregulate antioxidative genes and reduce oxidative stress. Finally, the liver shows decreased high mobility group box 1 and F4/80 + macrophages, suggesting an anti‐inflammatory response. This work provides a novel design strategy of nanozymes for ROS‐related disease treatment.