Copper/Carbon Hybrid Nanozyme: Tuning Catalytic Activity by the Copper State for Antibacterial Therapy

Metal-carbon hybrid materials have shown promise as potential enzyme mimetics for antibacterial therapy; however, the effects of metal states and corresponding antibacterial mechanisms are largely unknown. Here, two kinds of copper/carbon nanozymes were designed, with tuned copper states from Cu⁰ to Cu²⁺. Results revealed that the copper/carbon nanozymes exhibited copper state-dependent peroxidase-, catalase-, and superoxide dismutase-like activities. Furthermore, the antibacterial activities were also primarily determined by the copper state. The different antibacterial mechanisms of these two copper/carbon nanozymes were also proposed. For the CuO-modified copper/carbon nanozymes, the released Cu²⁺ caused membrane damage, lipid peroxidation, and DNA degradation of Gram-negative bacteria, whereas, for Cu-modified copper/carbon nanozymes, the generation of reactive oxygen species (ROS) via peroxidase-like catalytic reactions was the determining factor against both Gram-positive and Gram-negative bacteria. Lastly, we established two bacterially infected animal models, i.e., bacteria-infected enteritis and wound healing, to confirm the antibacterial ability of the copper/carbon nanozymes. Our findings provide a deeper understanding of metal state-dependent enzyme-like and antibacterial activities and highlight a new approach for designing novel and selective antibacterial therapies based on metal-carbon nanozymes.