A Dual-Window NIR-Responsive High-Entropy Oxide Nanozyme for Photothermal-Catalytic Synergistic Therapy of Drug-Resistant Bacterial Wounds
Chronic infections caused by biofilms of drug-resistant bacteria pose a significant challenge in clinical treatment. Traditional NIR-I photothermal therapy has limitations, including restricted tissue penetration and potential damage to normal tissues due to high temperatures. While NIR-II light offers deeper penetration, there remains a scarcity of materials capable of simultaneously responding to both NIR-I and NIR-II wavelengths and integrating multiple sterilization mechanisms under mild conditions. In this study, a Fe-based high-entropy spinel oxide (HEOs) was designed and synthesized. Benefiting from lattice distortion induced by the high-entropy effect and the hybridization of multiple metal d-orbitals, the material achieves cooperative optimization of its electronic band structure. Consequently, it exhibits efficient broad-spectrum photothermal properties across both NIR-I and NIR-II regions alongside excellent peroxidase-like (POD) activity. Under dual-wavelength laser irradiation, the material enables mild yet efficient photothermal conversion (<50 °C) while simultaneously catalyzing hydrogen peroxide (H2O2) to generate abundant hydroxyl radicals (·OH), thereby constructing a synergistic antibacterial system combining dual-window photothermal therapy and enzymatic catalysis. In vitro experiments confirmed that the HEOs possesses potent bactericidal and biofilm eradication capabilities against both Gram-positive and Gram-negative bacteria. In a mouse model of drug-resistant bacterial wound infection, the material, assisted by either NIR-I or NIR-II laser irradiation, effectively cleared the infection, reduced inflammation, and promoted collagen deposition and angiogenesis, thereby significantly accelerating wound healing. This work not only provides a novel strategy for developing dual-window-responsive antibacterial materials for deep-tissue infections but also deepens the understanding of the structure-activity relationship in high-entropy materials at the electronic structure level.