SMart Nanoparticle–Hydrogel Hybrid System for Synergistic Eradication of Infection and Promotion of Wound Healing

Abstract This study develops an efficient and intelligent photothermal therapy (PTT) system for treating Staphylococcus aureus ‐infected wounds by integrating a multifunctional hydrogel (PAOC‐3@BA) with S. aureus ‐targeted photothermal nanoparticles (Fe 2 O 3 ‐CS@RBP). The Fe 2 O 3 ‐CS@RBP nanoparticles, functionalized with receptor‐binding proteins (RBP) from bacteriophages, selectively recognize S. aureus and generate localized heat under near‐infrared (NIR) irradiation for precise bacterial eradication. PAOC‐3 hydrogel, loaded with the anti‐inflammatory agent baicalin (BA), has a cloud point temperature (T cp ) of ≈47 °C and exhibits strong tissue adhesion and heat‐induced contraction. Upon NIR‐triggered heating, the hydrogel undergoes a turbidity transition, forming a light‐scattering barrier that limits further NIR penetration and maintains a stable therapeutic temperature. This feedback mechanism enhances antibacterial efficacy while preventing tissue overheating. Simultaneously, the hydrogel's high tissue adhesion and contractile behavior promote wound closure and stimulate BA release to suppress inflammation. The system achieves rapid wound healing within one week, offering effective infection control and tissue regeneration. Overall, this work introduces a smart therapeutic platform that integrates bacterial targeting, self‐regulating photothermal therapy, tissue adhesion, and stimulus‐responsive drug release, providing a safe and effective strategy for treating bacterial skin infections.