CuCoO Nanoflowers with Multiple Enzyme Activities for Treating Bacterium-Infected Wounds via Cuproptosis-like Death.

Nanozyme-driven catalytic therapy provides a promising treatment strategy for bacterial biofilm-infected wounds. However, the single functionality and limited catalytic efficiency of nanozyme-based materials often restrict the effectiveness of wound infection treatment. In this study, CuCoO nanoflowers with multiple enzymatic activities were prepared for antibacterial/antibiofilm treatment by cuproptosis-like death. CuCoO exhibited peroxidase-like (POD-like) and oxidase-like (OXD-like) dual enzyme activities that generated large amounts of •OH and O. Moreover, the glutathione peroxidase-like (GSH-Px-like) activity of CuCoO was able to reduce the overexpression of GSH in the wound microenvironment, enhancing the therapeutic effects of reactive oxygen species (ROS). The morphology of CuCoO was modified using a hydrothermal method with PEG4000 as the solvent, resulting in the exposure of more active center sites and a significant improvement in enzyme catalytic activity. The in vitro results demonstrated the pronounced disruption effect of CuCoO on biofilms formed by bacteria. In vivo, CuCoO significantly promoted angiogenesis, collagen deposition, and cell proliferation. Transcriptome sequencing revealed that elevated ROS levels in bacteria led to cell membrane damage and metabolic disruption. In addition, Cu overload in bacteria induces lipid peroxidation accumulation and disrupts the respiratory chain and tricarboxylic acid (TCA) cycle, ultimately leading to bacterial cuproptosis-like death. This therapeutic strategy, which combines the synergistic effects of multiple enzyme-like activities with cuproptosis-like death, provides an approach for treating biofilm infections.