NIR-II-triggered copper single-atom catalyst depots coupling catalysis and drug release for infected chronic wounds...

Precise control of antimicrobial and immunomodulatory signals in both space and time is essential for addressing drug-resistant chronic wounds. Here, an NIR-II-responsive nanomedicine depot is created by integrating fasudil (FAS) into a copper single-atom catalyst scaffold (Cu SACs/FAS), which is formed through a coordination-constrained pyrolysis process. Under 1064-nm irradiation, Cu SACs/FAS couples photothermal heating with dual enzyme-mimicking activities (peroxidase-like catalysis and GSH depletion), producing reactive oxygen species (ROS) and copper-dependent bacterial stress consistent with cuproptosis-related injury. The porous framework enables on-demand, sustained FAS release, which promotes macrophage polarization toward a pro-angiogenic phenotype and mitigates excessive inflammation. The platform achieves broad-spectrum antibacterial activity against E. coli, S. aureus, and MRSA in vitro and accelerates closure with improved tissue quality in an MRSA-infected wound model in vivo with the supplementation of minimal exogenous H₂O₂. This study establishes a structure-function linkage between single-atom active sites, NIR-II-enhanced catalytic/photothermal coupling, and pore-regulated drug release, offering a materials-centric strategy for simultaneous infection control and immune-guided repair.