Ir(IV) and Ir(III) in situ transition promotes ROS generation for eradicating multidrug-resistant bacterial infection

Whether reactive oxygen species are a consequence or a cause of antibacterial activity is not fully known. A glutathione (GSH)-mediated oxidative defense mechanism is an important factor against bacterial infection. Reactive oxygen species (ROS) storm-mediated bacterial death by depleting GSH is also considered an effective strategy. Therefore, we designed and synthesized hybrid iridium ruthenium oxide nanozymes (IrRuO NPs), where IrRuO NPs alternately consume GSH through double redox electron pair auto-valent cycles, while an IrRuO NP-mediated Fenton-like reaction occurs to realize an ROS storm, which in turn mediates lipid peroxidation to promote bacterial death. The results showed that IrRuO NPs can effectively inhibit and kill Gram-positive and Gram-negative bacteria in vitro, and can be used as broad-spectrum antibiotics. Importantly, the wound and sepsis models of MRSA infection confirmed the efficient antibacterial activity of IrRuO NPs in vivo. Accordingly, this study provides a new idea for metal oxide hybrid nanoenzymes and their biological functions.