Atomic‐Precision NiCo Dual‐Atom Nanozybiotic for Drug‐Resistant Infections and Tissue Repair

ABSTRACT The accelerated emergence of drug‐resistant bacteria and superbugs presents a critical challenge to conventional antibiotic therapies for infectious diseases. Therefore, the development of alternative antibacterial agents is imperative to effectively combat drug‐resistant bacteria and their associated infections. A nitrogen‐doped carbon hollow prismatic nanozybiotic bearing NiCo SACs that integrates peroxidase‐like catalysis with NIR‐II (1064 nm) photothermal conversion for multi‐mechanistic antibacterial therapy is engineered. Synchrotron XAFS and DFT resolve heteronuclear Ni‐Co sites and reveal electronic synergy that lowers intermediate barriers and enhances catalytic efficiency. NiCo SACs trigger ROS‐mediated damage, suppress bacterial metabolism, and modulate the inflammatory microenvironment, achieving biofilm clearance of 94.67% ( MRSA ) and 87.05% ( E. coli ). Transcriptomics shows disruption of oxidative phosphorylation and downregulation of resistance genes, clarifying the mode of action. In vivo, NiCo SACs eradicate pathogens, reduce cytokines, accelerate wound closure, and protect joints in mouse wound infection and rat septic arthritis models, with good biocompatibility. This atomic‐precision, dual‐atom platform advances nanozymes from concept to deep‐tissue, combination antibacterial therapy, offering a generalizable strategy to combat multidrug‐resistant infections while promoting tissue repair.