Cobalt Single-Atom Nanozyme-Berberine Nanoplatform for Photothermal–Catalytic Synergistic Modulation of Oxidative Stress and Inflammatory Microenvironment in Bacterial-Infected Wounds

Abstract Bacterial-infected wounds remain an intractable global health issue due to the escalation of antibiotic resistance and the dysregulated inflammatory microenvironment, while conventional therapies fail to achieve antibacterial and anti-inflammatory effects simultaneously. Herein, a multifunctional cobalt single-atom nanozyme-berberine (Co SA/B) nanoplatform is fabricated for bacterial-infected wound repair, integrating the multi-enzyme catalytic and photothermal properties of single-atom nanozymes with the natural bioactivities of berberine (BBR). The atomically dispersed Co sites endow the platform with multiple enzyme-like activities to trigger reactive oxygen species generation, bacterial glutathione depletion, and wound hypoxia relief, thereby eliminating pathogens via oxidative stress. Under 808 nm laser irradiation, the Co SA carbon matrix exhibits prominent photothermal performance, realizing photothermal therapy and further boosting catalytic activity. Loaded BBR synergistically reinforces antibacterial efficacy and modulates the inflammatory microenvironment by inducing M1-to-M2 macrophage repolarization, relieving local inflammation, and promoting tissue regeneration. In vitro experiments verify that Co SA/B combined with a near-infrared (NIR) laser efficiently eradicates Staphylococcus aureus (S. aureus) and Escherichia coli, disrupts bacterial biofilms/membranes with negligible cytotoxicity to normal cells. In vivo evaluations of a S. aureus-infected mouse abscess model confirm that Co SA/B achieves photothermal–catalytic synergistic therapy, significantly inhibiting bacterial colonization, alleviating inflammatory infiltration, and promoting epidermal regeneration and collagen deposition, with excellent in vivo biosafety. This work initiates the combination of single-atom nanozymes and natural herbal bioactive ingredients to synergistically tune oxidative stress levels and the inflammatory microenvironment, presenting an antibiotic-free intervention for bacterial-infected wound repair.