Bacterial Infection Microenvironment Sensitive Prodrug Micelles With Enhanced Photodynamic Activities For Infection Control

Because of the severe antibiotic resistance, photodynamic therapy is considered as a potent method for the treatment of bacterial infection with bare drug resistance. However, its therapeutic efficacy is not always satisfactory in practical treatment. In this study, pH-responsive prodrug micelles were prepared by conjugation of chlorin e6 to polyethylene glycol-b-poly(2-(hexamethyleneimino) ethyl methacrylate-co-aminoethyl methacrylate) for improving the antimicrobial activity of photodynamic therapy. The micelles were negatively charged in normal physiological environment, which was very important for long blood circulation. However, the micelles could turn to be positively charged in bacterial infection microenvironment and then adhere to negatively charged bacterial membranes, which could significantly improve their antibacterial activity against both methicillin-resistant Staphylococcus aureus and Escherichia coli after laser irradiation. The in vivo experiment showed excellent antibacterial effect of pH-sensitive micelles in a subcutaneous infection model. The micelles showed great potential in the photodynamic therapy of stubborn bacterial infections.