Spindle-Shaped Multifunctional Nanozymes with NIR-Enhanced Catalytic Activity for Treating Methicillin-Resistant Staphylococcus aureus (MRSA)-Infected Wounds through Bacterial Cuproptosis-like Death.

Methicillin-resistant Staphylococcus aureus (MRSA) wound infections remain a significant global challenge and demand new-generation biomaterials to eliminate bacterial infections and promote rapid wound healing. Although the nanozyme is a promising approach, the restricted unimodal bactericidal functionality hinders its efficacy in treating complex wound infections. In this study, copper-tannic acid (Cu-TA) nanozymes (NMs) with multifunctional properties were developed for the treatment of bacterial infections and biofilms via cuproptosis-like cell death. The as-prepared Cu-TA demonstrated peroxidase-like (POD-like) activity, generating substantial amounts of hydroxyl radicals (•OH). In vitro studies revealed that Cu-TA efficiently disrupted bacterial biofilms, while in vivo experiments demonstrated its ability to promote anti-inflammatory responses, angiogenesis, collagen synthesis, and cellular proliferation. Transcriptome sequencing revealed that bacterial reactive oxygen species (ROS) caused damage to the cell membrane and disrupted metabolic processes. Furthermore, copper overload triggered lipid peroxidation (LPO) buildup and interfered with the tricarboxylic acid (TCA) cycle, culminating in cuproptosis-like bacterial death. Overall, this study successfully developed a spindle-shaped, multifunctional nanozyme for combating bacterial infections through cuproptosis-like cell death while promoting infected wound healing. The results validate the clinical potential of Cu-TA NMs for treating MRSA-infected wounds.