Cholesterol-Functionalized Metal–Phenolic Network Nanoparticles for Antibacterial Chemodynamic Therapy

Although antibacterial chemodynamic therapy (CDT) has become as a promising nonantibiotic approach, its therapeutic efficacy is often limited by excessive glutathione (GSH) and by insufficient bacterial binding. Herein, we report a cholesterol-functionalized metal–phenolic network (MPN), denoted as CNT-CH, to simultaneously overcome both limitations. CNT-CH was prepared via a facile one-step coordination-driven assembly method, in which Cu 2+ simultaneously chelated with cholesterol-functionalized tannic acid (TA-CH) and naphthazarin (Nap). In CNT-CH, the cholesterol segment enhances its affinity toward bacterial membrane. Under mildly acidic infectious sites, partial disassembly of CNT-CH leads to the release of Cu 2+, which is reduced to Cu + by TA-CH for hydroxyl radicals (·OH) production. As a GSH scavenger, Nap amplifies the · ·OH-mediated damage. The integration of cholesterol-enabled enhanced bacterial adhesion, Cu + -driven CDT, and Nap-mediated GSH depletion provides a combinatorial CDT nanoplatform. Both in vitro and in vivo experiments verified its enhanced bacterial eradication. This multifunctional MPN-based strategy offers a promising and efficient platform for developing antibacterial nanomedicines against bacterial infections.