Self-Assembly and Disassembly of Glycol Chitosan/Photosensitizer Nano-Micelles for Antibacterial Photodynamic Therapy

Creating an efficient antimicrobial photodynamic therapy (PDT) method while reducing the difficulty of preparation and operation is much anticipated but challenging. In this research, we facilely developed glycol chitosan (GC)/protoporphyrin IX (PpIX) nano-micelles for effective photodynamic inactivation of Gram-positive bacteria. The mixture of glycol chitosan (GC) and protoporphyrin IX (PpIX) self-assembled into positively charged GC/PpIX nano-micelles through hydrophobic interaction and electrostatic interaction. GC/PpIX nano-micelles significantly improved singlet oxygen generation, and notably enhanced the antibacterial PDT effect toward Gram-positive bacteria in a preincubation-free manner without developing drug resistance. Upon binding to the bacterial cells through electrostatic interaction, GC/PpIX nano-micelles were disassembled, leaving GC on the bacterial surface, inducing bacterial cell aggregation and acting like a glue to coat the bacterial surface and release PpIX into the cells, generating singlet oxygen under light irradiation to impair DNA. Collectively, the easy construction of GC/PpIX nano-micelles offers a modality for effective antibacterial PDT with simple operation and without drug resistance development, benefiting the treatment of Gram-positive bacterial infections in clinic.