Bacteria‐Targeted Single‐Atom Nanozyme With Photothermal‐Augmented Multi‐Enzymatic Cascade and NO Delivery for Enhanced Infected Wound Healing

Abstract Infected diabetic wound management confronts significant challenges, including bacterial resistance, oxidative stress, and impaired vascular repair, resulting in substantial unmet clinical needs. To address these issues, a multifunctional therapeutic nanoplatform, mCu‐SAE@BNN6@PEG‐Van (CBPV), is developed by sequentially functionalizing mesoporous copper single‐atom nanozymes (mCu‐SAE) loaded with the nitric oxide (NO) donor BNN6 and vancomycin‐conjugated polyethylene glycol (PEG‐Van). CBPV integrates three synergistic therapeutic modalities: 1) pathogen‐specific targeting via Van‐mediated bacterial recognition; 2) NIR‐II photothermally enhanced catalytic therapy via Cu‐N 3 centers in mCu‐SAE, generating reactive oxygen species; 3) photoactivated NO release from BNN6, enabling peroxynitrite (ONOO − ) formation through radical coupling. Irradiation of CBPV with a 1064‐nm laser simultaneously enables deep‐tissue photothermal activation, thermally boosted chemodynamic activity, and controlled NO liberation. In vitro and in vivo studies demonstrate that CBPV exhibits remarkable antibiofilm activity and antibacterial efficacy against methicillin‐resistant Staphylococcus aureus (99.6% inactivation) while promoting angiogenesis through NO‐mediated endothelial cell activation. Both epidermal wound and subcutaneous cyst models show accelerated healing with enhanced collagen deposition and neovascularization. By integrating bacterial targeting with NIR‐II‐responsive therapeutic cascades, this work establishes a spatiotemporally controlled therapeutic paradigm that simultaneously addresses infection control and tissue regeneration in chronic wounds, offering a promising translational strategy for managing complex diabetic wounds.