Dynamic Antibacterial-to-Regenerative Switching via NIR/Visible Light Activation: Copper Single-Atom Nanozyme with...

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 CO₂ 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.