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 <i>Escherichia coli</i> (<i>E. coli</i>) and <i>Staphylococcus aureus</i> (<i>S. aureus</i>) at 60 μg/mL, achieving complete eradication. Moreover, CSPC eliminated 65.90 ± 3.46% of the <i>S. aureus</i> biofilm under near-infrared (NIR) irradiation. <i>In vivo</i> 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.