Super-Stable Chitosan-Based Nanoparticles for Broad-Spectrum Antimicrobial Photodynamic Therapy

Establishing antimicrobial photodynamic therapy (PDT) approaches to enhance antimicrobial activities of insoluble photosensitizers in terms of their solubility, stability, and safety is highly desirable yet challenging. Here, we reported super-stable carboxymethyl chitosan-polyethyleneimine-protoporphyrin IX nanoparticles (CMCS-PEI-PpIX NPs) for effective photodynamic inactivation of bacteria and fungi with excellent biocompatibility. CMCS-PEI-PpIX self-assembled into NPs in solution with significantly improved singlet oxygen generation. Consequently, NPs exhibited exceptional photoinactivation toward a broad range of microbes with record low minimal bactericidal concentrations. NPs were highly stable after 28 days of storage. Furthermore, NPs exhibited negligible cytotoxicity without hemolysis on red blood cells. NPs can efficiently attach to the microbial cell through electrostatic interaction to generate singlet oxygen with light irradiation, which caused severe damage to the cell membrane, causing microbial cell death. Overall, the development of CMCS-PEI-PpIX NPs provides a route for improving the microbicidal PDT efficacy, benefiting the clinic treatment of microbial infections.