Off-Photosensitizing Derived Immuno-Photodynamic Therapy toward Postoperative Care

Immuno-photodynamic therapy (IPDT) has emerged as a promising cancer treatment strategy. However, conventional IPDT faces challenges related to post-treatment safety, owing to the use of residual photosensitizers (PSs). In this study, on a novel H₂O₂-responsive aggregation-induced emission PS is reported, TBZPYBE, designed to selectively target cancer cells and enhance the therapeutic efficacy and postoperative safety of IPDT. Although TBZPYBE exhibits weak fluorescence, strong reactive oxygen species (ROS) are produced under light irradiation, demonstrating its high photodynamic therapy (PDT) efficacy in vitro and in vivo. Following PDT, TBZPYBE underwent self-quenching in the presence of H₂O₂, converting it to TBZPY, which exhibits strong fluorescence but reduced ROS generation. Simultaneously, quinone methide, a glutathione scavenger that amplifies PDT efficiency, is released. Furthermore, TBZPYBE activated the immune response by promoting dendritic cell maturation and polarizing M2 to M1 macrophages. The observed IPDT effects of TBZPYBE can be attributed to tumor selectivity, self-quenching mechanisms, and the ability to trigger immune responses, offering a balanced cancer treatment approach with improved post-treatment safety.