Zwitterionic Photosensitizer‐Assembled Nanocluster Produces Efficient Photogenerated Radicals via Autoionization for Superior Antibacterial Photodynamic Therapy
Ping He, Mingxuan Jia, Linfang Yang, Haolin Zhang, Ruizhe Chen, Weiyun Yao, Yonghui Pan, Quli Fan, Wenbo Hu, Wei Huang
Abstract
Abstract Photodynamic therapy (PDT) holds significant promise for antibacterial treatment, with its potential markedly amplified when using Type I photosensitizers (PSs). However, developing Type I PSs remains a significant challenge due to a lack of reliable design strategy. Herein, a Type I PS nanocluster is developed via self‐assembly of zwitterionic small molecule (C3TH) for superior antibacterial PDT in vivo. Mechanism studies demonstrate that unique cross‐arranged C3TH within nanocluster not only shortens intermolecular distance but also inhibits intermolecular electronic‐vibrational coupling, thus facilitating intermolecular photoinduced electron transfer to form PS radical cation and anion via autoionization reaction. Subsequently, these highly oxidizing or reducing PS radicals engage in cascade photoredox to generate efficient ·OH and O 2 ‾·. As a result, C3TH nanoclusters achieve a 97.6% antibacterial efficacy against MRSA at an ultralow dose, surpassing the efficacy of the commercial antibiotic Vancomycin by more than 8.8‐fold. These findings deepen the understanding of Type I PDT, providing a novel strategy for developing Type I PSs.