Achieving superior therapeutic effects on methicillin-resistant Staphylococcus aureus infection via simple sulfonation process for preparing zwitterionic photosensitizer

Drug-resistant bacterial biofilm-associated infections pose a significant threat to human health, as the physical barrier and protective matrix of biofilms enable bacterial evasion of antibiotic effects, leading to refractory infections. To address this challenge, we develop a novel photosensitizer PY and its sulfonated zwitterionic derivative PYSO 3 . Both photosensitizers exhibit aggregation-induced emission (AIE) properties coupled with exceptional photodynamic and photothermal performance in aggregates. Sulfonated zwitterionic modification significantly enhance the biological activity of PYSO 3 , demonstrating potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and mature biofilms under laser irradiation. Mechanistically, PYSO 3 -mediated combinational photodynamic therapy and photothermal therapy disrupt critical bacterial survival pathways, including quorum sensing systems, glycolysis/gluconeogenesis pathways, and oxidative stress homeostasis, thereby inhibiting normal bacterial metabolism and biofilm formation. In vivo experiments reveal remarkable antibacterial performance with accelerated wound healing rates and favorable biosafety profiles. This AIE-active zwitterionic photosensitizer not only holds great promise for combating MRSA infections but also provides new design strategies for developing multifunctional antimicrobial agents targeting drug-resistant pathogens.