Glutathione-responsive oxidative stress nanoamplifier boosts sonodynamic/chemodynamic synergistic antibacterial...

To address adverse effects such as specific hypoxia, rapid depletion of endogenous hydrogen peroxide (H₂O₂), and overexpressed glutathione (GSH) in the bacterial microenvironment on reactive oxygen species (ROS)-based antibacterial strategies, this study developed a GSH-responsive oxidative stress nanoamplifier (MPPC) by self-assembly of polyethylene glycol modified mesoporous polydopamine (MPDA-PEG), protoporphyrin IX (PPIX), and copper ion (Cu²⁺). MPPC enhances ROS-mediated sonodynamic (SDT) and chemodynamic therapy (CDT) by supplying H₂O₂ and depleting GSH. PPIX generates hydroxyl radicals (·OH) and singlet oxygen (¹O₂) under ultrasound for SDT, while MPDA-PEG acts as a nanocarrier and electron donor, producing H₂O₂ and consuming GSH. Cu²⁺ is reduced to Cu⁺ by GSH, enabling Fenton-like reactions to convert H₂O₂ into ·OH for CDT while alleviating hypoxia. This synergistic strategy amplifies oxidative stress, achieving potent antibacterial and anti-biofilm effects. In vivo studies demonstrate effective therapeutic efficacy in infected wound along with ideal biocompatibility, showcasing MPPC as a promising therapeutic platform for bacterial wound infections.