NIR-Responsive Nanoplatform Based on CuO2 with Self-Supplied H2O2/O2 for Synergistic Photodynamic-Chemodynamic-Photothermal Therapy of Skin Abscesses.

Chemodynamic therapy (CDT) and photodynamic therapy (PDT) have emerged as promising strategies for treating skin abscesses. However, their therapeutic efficacy is fundamentally constrained by the hypoxic and hydrogen peroxide-deficient microenvironment characteristic of abscesses. Herein, we developed a near-infrared (NIR) light-responsive nanoplatform (ICG/CuO2@PCM) by encapsulating copper peroxide (CuO2) and indocyanine green (ICG) within a phase-change material (PCM), which enables control over self-supplied H2O2/O2 release via an NIR-triggered cascade. Upon irradiation, ICG-mediated photothermal conversion elevates the temperature beyond the PCM melting threshold, triggering a burst release of CuO2 and ICG. CuO2 generates hydroxyl radicals (•OH) through a Fenton-like reaction in the acidic wound microenvironment. Additionally, CuO2 can thermally decompose under photothermal conditions to produce a sustained oxygen supply, which ICG immediately converts into singlet oxygen (1O2), thereby enhancing PDT efficiency. Furthermore, photothermal therapy not only enhances the efficiency of CDT but also provides additional antibacterial support. Remarkably, ICG/CuO2@PCM (NPs), coupled with irradiation, accelerate abscess wound recovery by dispersing biofilm, killing bacteria, and promoting macrophage polarization toward an anti-inflammatory phenotype. Overall, this NIR-responsive nanoplatform highlights the promise in controlled modulation of microenvironment-adaptive antimicrobial strategies to overcome current limitations of hypoxic infections.