Electronic Interactions in Co/Cu Biotomic Nanozymes for Catalytic Eradication of Gram-Positive Bacterial Biofilms

Biofilm-associated infections caused by Gram-positive pathogens remain highly resistant to conventional antibiotic therapy due to restricted drug penetration and persistent inflammatory microenvironments. Inspired by the catalytic versatility and biocompatibility of cobalt, a series of cobalt-based diatomic nanozymes were rationally engineered for catalytic antibacterial therapy. Among them, cobalt/copper diatomic nanozymes (Co/Cu-DAzymes) exhibited the most pronounced antibacterial and antibiofilm activities. Structural characterization supports the presence of highly dispersed Co and Cu coordination sites, while DFT calculations based on an idealized adjacent Co-Cu model suggest that heteronuclear electronic interactions may facilitate H₂O₂ activation and ROS generation.Co/Cu-DAzymes achieve more than 95% antibacterial efficiency against both Group A Streptococcus (GAS) and Staphylococcus aureus, while inhibiting biofilm formation by over 80%, with negligible cytotoxicity in vitro and in vivo. In a murine GAS-infected wound model, treatment with Co/Cu-DAzymes combined with low-dose H₂O₂ significantly accelerated wound closure and was associated with histological features of more advanced tissue repair. These findings highlight the potential contribution of heteronuclear electronic interactions to catalytic H₂O₂ activation and provide a plausible design basis for developing antibacterial dual-metal nanozymes.