Photodynamic therapy combined with quaternized chitosan antibacterial strategy for instant and prolonged bacterial infection treatment

Abstract

Drug-resistant bacterial infections represent a critical global public health challenge, driven largely by the misuse and overuse of antibiotics. Tackling the growing threat of bacterial resistance necessitates the development of innovative antibacterial agents that function independently of traditional antibiotics. In this study, novel antibacterial nano-micelles were rationally designed by conjugating quaternized chitosan with the photosensitizer chlorin e6. These nano-micelles promoted the solubility and stability of chlorin e6 while maintaining robust singlet oxygen generation under 660 nm laser irradiation. The positively charged nano-micelles facilitated strong electrostatic interactions with bacterial surfaces, promoting efficient adhesion and enabling effective photodynamic antibacterial activity mediated by singlet oxygen. In vitro experiments revealed that the nano-micelles exhibited instant and prolonged antibacterial effects, effectively suppressing bacterial proliferation without inducing resistance and disrupting mature biofilms. Furthermore, in conjunction with laser treatment, nano-micelles exhibited remarkable in vivo antibacterial efficacy, significantly accelerating the healing of skin wounds infected with Methicillin-resistant Staphylococcus aureus while maintaining favorable biocompatibility. These findings highlight the potential of the nano-micelles as a promising non-antibiotic antibacterial formulation, offering a powerful strategy to combat drug-resistant bacterial infections and paving the way for their clinical application in infection management.