Copper-doped carbon dots nanozymes with dual peroxidase/catalase activities for synergistic ROS-mediated ultra-potent MRSA eradication and wound healing.

Methicillin-resistant Staphylococcus aureus (MRSA) infections threaten global public health, demanding innovative antibiotic-free antibacterial strategies to overcome conventional therapeutic limitations. Herein, copper-doped carbon dots (Cu-CDs) were synthesized via a facile one-pot hydrothermal method, featuring dual peroxidase (POD)- and catalase (CAT)-like nanozyme activities. In vitro antibacterial assays demonstrated concentration-dependent MRSA eradication, with minimum bactericidal concentrations (MBCs) of 1.0 μg/mL for Cu-CDs alone and 0.25 μg/mL for Cu-CDs in combination with H2O2, yielding antibacterial efficacy 2048-fold more potent than vancomycin. Mechanistic studies elucidated a four-stage synergistic bactericidal process: (i) electrostatic adsorption /biofilm disruption; (ii) reactive oxygen species (ROS) -mediated cell membrane damage; (iii) intracellular ·OH generation and Cu+-induced bacterial DNA breaks; and (iv) metabolic/antioxidant system collapse with dysregulated drug-resistant (mecA) and cell division genes. Cu-CDs exhibited exceptional biocompatibility (L929 viability >95% at 150 μg/mL; hemolysis <5% at 50 μg/mL). In MRSA-infected mouse wounds, Cu-CDs + H2O2 achieved ∼92% closure by day 7, with intact epidermis and no organ pathology. This work establishes Cu-CDs as a high-performance nanozyme platform for antibiotic-free MRSA therapy, advancing nanozyme clinical translation.