Light-Activatable Nanotherapeutic Platform Synchronizing ROS-Mediated Antibacterial Action with Macrophage Polarization for Refractory Wound Infections.

The treatment of persistent drug-resistant bacterial infections in wounds poses a significant global medical challenge. Developing innovative antimicrobial strategies capable of simultaneously achieving bacterial eradication, inflammation resolution, and tissue regeneration has become imperative. Herein, a nanocomposite featuring plasma-enhanced enzymatic activity and immunoregulatory properties is engineered, designed to reprogram the wound microenvironment and expedite healing in drug-resistant bacterial infections. Capitalizing on the localized surface plasmon resonance effect of Au@Ag nanoparticles coupled with the pH-dependent peroxidase-like (POD-like) activity of cerium dioxide (CeO2), the BSA-(Au@Ag/CeO2) nanocomposites orchestrate dual-modality photothermal-chemodynamic therapy for enhanced bactericidal efficacy and biofilm disruption. Upon near-infrared laser irradiation, plasmon-generated hot electrons are transferred to CeO2, triggering massive reactive oxygen species production via enhanced POD-like catalysis. This synergistic dual-action mechanism eradicates methicillin-resistant Staphylococcus aureus (MRSA) through membrane disruption and reactive oxygen species (ROS)-induced oxidative stress. Remarkably, the nanosystem not only suppresses proinflammatory cytokine storms but also steers macrophage polarization toward tissue reparative M2 phenotypes at infection sites, thereby alleviating pathological inflammation and fostering regenerative microenvironments. Biosafety assessments confirm the absence of discernible toxicity in vital organs. This multifunctional platform represents a paradigm-shifting strategy for managing antibiotic-resistant wound infections, providing a clinically translatable solution to combat antimicrobial resistance.