GSH-Depleting and H2O2 Self-Supplying Calcium Peroxide-Based Nanoplatforms for Efficient Bacterial Eradication via Photothermal-Enhanced Chemodynamic Therapy

Chemodynamic therapy (CDT), an innovative approach for treating bacterial infections, has garnered significant attention due to its ability to generate hydroxyl radicals (•OH) via Fenton/Fenton-like reactions. However, the effectiveness of CDT is considerably hindered by the limited availability of endogenous hydrogen peroxide (H₂O₂) and the overexpression of glutathione (GSH) within the infection microenvironment. To address these limitations, a multifunctional nanoplatform with self-supplying H₂O₂, GSH-depletion properties, and photothermal properties was developed through a straightforward and mild strategy. This platform employs calcium peroxide (CaO₂) as the core, coated with silica (SiO₂) to enhance stability and further modified with a Cu(II)-doped polydopamine (PDA) layer, forming a core-shell structured CaO₂@SiO₂@PDA-Cu (CSPC). The Cu(II) released by CSPC, combined with the H₂O₂ produced from CaO₂ degradation, participates in a Fenton-like reaction to generate toxic •OH radicals. Additionally, Cu(II)-mediated redox reactions deplete overexpressed GSH, thereby enhancing CDT efficacy. Upon coordination with Cu(II), the photothermal properties of PDA are significantly enhanced, achieving a photothermal conversion efficiency of up to 43%. The hyperthermia induced by photothermal therapy (PTT) further increases •OH production, augmenting CDT. The CSPC nanomaterials demonstrated outstanding synergistic photothermal bactericidal activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) at 60 μg/mL, achieving complete eradication. Moreover, CSPC eliminated 65.90 ± 3.46% of the S. aureus biofilm under near-infrared (NIR) irradiation. In vivo experiments demonstrated that CSPC treatment effectively eradicated bacteria, with a bacterial survival rate of 6.56 ± 3.28%, and accelerated wound healing, reducing the relative wound size to 7.0 ± 2.6%. Therefore, this study successfully developed versatile nanomaterials that significantly enhance the PTT/CDT dual-mode antibacterial performance.