NIR-triggered in situ self-supplied H2O2 for boosting photothermal disinfection via CuO2-mediated catalytic cascade reaction

Herein, we constructed a near-infrared (NIR) responsive CuS/CuO₂ cascade nanozyme system addressing the critical limitation of exogenous H₂O₂ dependency in conventional therapies. This system incorporates NIR-responsive antibacterial CuS/CuO₂ composite based on cascade nanoenzymes. The loaded CuO₂ nanoparticles (NPs) spontaneously generate Cu²⁺ and H₂O₂ in situ upon NIR irradiation (808 nm). This initiates a dual catalytic pathway: (1) Cu²⁺-mediated Fenton-like reactions and (2) H₂O₂-activated peroxidase-like activity, synergistically producing ·OH radicals (EPR-confirmed). Under NIR irradiation, CuO₂ releases H₂O₂ that activates the peroxidase-like activity of CuS. During the following cascade reaction, Cu²⁺ catalyzes a Fenton-like reaction to produce a large amount of ·OH, while H₂O₂ activates peroxidase-like activity in the CuS/CuO₂ composite. Additionally, CuS/CuO₂ also exhibits oxidase-like activity. The oxidase-like activity coupled with the cascade reaction simulated with photothermal conditions allows CuS/CuO₂ (100 μg/mL) to effectively destroy Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Methicillin-resistant Staphylococcus aureus (MRSA). Moreover, the CuS/CuO₂ composite effectively inhibits the formation of biofilms of E. coli, S. aureus, and MRSA. ·OH was confirmed to be the main free radical during the antimicrobial process of CuS/CuO₂. In vivo anti-infection assays prove that CuS/CuO₂ could accelerate wound healing under NIR irradiation with negligible toxicity. This self-sustaining system eliminates exogenous H₂O₂ requirements while achieving combinatorial antimicrobial efficacy through photothermal-potentiated nanozyme cascades.