Synergistic Sunlight-Activated Photodynamic and Near-Infrared-Induced Mild Photothermal Therapy for Infected Wound...

Bacterial infection-associated inflammation and drug resistance severely impede effective wound healing. Herein, we report a multifunctional Bi₂WO₆:Yb,Er@CuS@CS nanoplatform that integrates photodynamic therapy (PDT), near-infrared (NIR)-triggered mild photothermal therapy (PTT), and Cu^{2 +} release for infected wound repair. Yb³⁺/Er³⁺ codoping endows Bi₂WO₆ with broadened visible-NIR light absorption and enhanced charge separation, enabling efficient reactive oxygen species generation under simulated sunlight. Surface-decorated CuS nanoparticles provide robust photothermal conversion under NIR irradiation, while chitosan modification improves biocompatibility and antibacterial performance. The nanoplatform exhibits > 99% antibacterial efficacy against both Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli and effectively disrupts bacterial biofilms under combined light activation. Importantly, precisely controlled NIR-induced mild thermal therapy (≈42°C) reprograms macrophage polarization from a proinflammatory M1 phenotype toward a reparative M2 phenotype. Transcriptomic analysis reveals that this immunomodulatory effect is associated with the downregulation of PI3K-Akt, TNF, and NF-κB signaling pathways. In vivo studies using MRSA-infected wound models demonstrate accelerated wound healing, enhanced angiogenesis, collagen deposition, and minimal systemic toxicity. This work presents a sunlight/NIR-activated therapeutic strategy that bridges antibacterial treatment and immune-regulated tissue regeneration for infected wound healing.