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

ABSTRACT 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 H 2 O 2 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 H 2 O 2 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 H 2 O 2 activation and provide a plausible design basis for developing antibacterial dual‐metal nanozymes.