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

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.