GSH-Depleting\nand H<sub>2</sub>O<sub>2</sub> Self-Supplying\nCalcium Peroxide-Based Nanoplatforms for Efficient Bacterial Eradication\nvia Photothermal-Enhanced Chemodynamic Therapy

Chemodynamic therapy (CDT), an innovative\napproach for treating\nbacterial infections, has garnered significant attention due to its\nability to generate hydroxyl radicals (•OH) via Fenton/Fenton-like\nreactions. However, the effectiveness of CDT is considerably hindered\nby the limited availability of endogenous hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and the overexpression of glutathione (GSH)\nwithin the infection microenvironment. To address these limitations,\na multifunctional nanoplatform with self-supplying H<sub>2</sub>O<sub>2</sub>, GSH-depletion properties, and photothermal properties was\ndeveloped through a straightforward and mild strategy. This platform\nemploys calcium peroxide (CaO<sub>2</sub>) as the core, coated with\nsilica (SiO<sub>2</sub>) to enhance stability and further modified\nwith a Cu(II)-doped polydopamine (PDA) layer, forming a core–shell\nstructured CaO<sub>2</sub>@SiO<sub>2</sub>@PDA-Cu (CSPC). The Cu(II)\nreleased by CSPC, combined with the H<sub>2</sub>O<sub>2</sub> produced\nfrom CaO<sub>2</sub> degradation, participates in a Fenton-like reaction\nto generate toxic •OH radicals. Additionally, Cu(II)-mediated\nredox reactions deplete overexpressed GSH, thereby enhancing CDT efficacy.\nUpon coordination with Cu(II), the photothermal properties of PDA\nare significantly enhanced, achieving a photothermal conversion efficiency\nof up to 43%. The hyperthermia induced by photothermal therapy (PTT)\nfurther increases •OH production, augmenting CDT. The CSPC\nnanomaterials demonstrated outstanding synergistic photothermal bactericidal\nactivity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) at 60 μg/mL, achieving\ncomplete eradication. Moreover, CSPC eliminated 65.90 ± 3.46%\nof the S. aureus biofilm under near-infrared\n(NIR) irradiation. <i>In vivo</i> experiments demonstrated\nthat CSPC treatment effectively eradicated bacteria, with a bacterial\nsurvival rate of 6.56 ± 3.28%, and accelerated wound healing,\nreducing the relative wound size to 7.0 ± 2.6%. Therefore, this\nstudy successfully developed versatile nanomaterials that significantly\nenhance the PTT/CDT dual-mode antibacterial performance.