Dynamic Antibacterial‐to‐Regenerative Switching via NIR/Visible Light Activation: Copper Single‐Atom Nanozyme with CO‐Mediated Scarless Healing for Chronic Diabetic Wounds

Abstract Poor healing of diabetic wounds is critically hindered by multidrug‐resistant biofilm infections and persistent inflammation, highlighting the need for precise therapeutic strategies that dynamically modulate the wound microenvironment to simultaneously achieve antibacterial, anti‐inflammatory, and pro‐angiogenic functions. A phenylboronic acid‐functionalized copper single‐atom nanozyme (PBA‐Cu SAzyme) is engineered that dynamically adapts to the wound microenvironment, enabling spatiotemporally controlled “antibacterial‐to‐regenerative” switching via dual‐light activation (NIR/visible light). In the infected microenvironment, the SAzyme activates peroxidase/glutathione oxidase‐like activities, generating ROS and depleting antioxidants for potent antibacterial effects. Concomitantly, the C─N coordination confers under mild NIR irradiation (808 nm) to intensify antibacterial activity by triggering intracellular copper aggregation and inducing bacterial cuproptosis‐like death. Crucially, visible light (400–700 nm) photocatalytically converts endogenous CO ₂ to CO, enabling spatiotemporal gas therapy: high local CO concentrations within infected zones synergize with antibacterial effects, whereas the diffused low‐dose CO in cleared areas resolves inflammation and stimulates angiogenesis, orchestrating the functional transition. In multidrug‐resistant P. aeruginosa ‐infected diabetic rats, this dynamically modulated strategy achieves rapid, near‐scarless healing by disrupting biofilms, dampening pro‐inflammatory cytokines (e.g., TNF‐α), robustly stimulating vascularization, and remodeling collagen. This work seamlessly integrates adaptive nanozyme catalysis with gas therapy, dynamically coordinating infection eradication with microenvironment‐driven tissue regeneration for chronic wound management.