Engineering Metal–Organic Framework System for Light-Free Antibacterial Photodynamic Therapy

Photodynamic therapy (PDT) offers a nonantibiotic alternative by leveraging light-activated photosensitizers (PSs) to generate reactive oxygen species (ROS) with strong bactericidal activity for bacterial elimination. However, the limited tissue penetration of external light and the hypoxic microenvironment at infection sites severely impair the therapeutic efficacy of PDT, hindering its clinical translation. In this nanosystem, glucose oxidase (GO<i>x</i>) loaded onto the MOF catalyzes glucose to generate hydrogen peroxide (H₂O₂), which subsequently reacts with manganese dioxide (MnO₂) in a cascade process. This cascade reaction alleviates hypoxia through O₂ production and activates luminol-based chemiluminescence (CL) to excite the embedded porphyrin photosensitizer (TCPP), enabling deep-tissue ROS generation without the additional external light. This self-sufficient activation strategy synergistically enhances the antibacterial efficacy by overcoming both light penetration and O₂ limitations. In a <i>Staphylococcus aureus</i> (<i>S. aureus</i>)-infected subcutaneous abscess models, the system achieves potent biofilm eradication and efficient bacterial clearance. By integrating oxygen self-supply, cascade enzymatic catalysis, and endogenous CL-triggered photosensitization into a single nanoplatform, this work presents a laser-free photodynamic therapy strategy against deep biofilm infections.