H ‐Aggregated Cationic Isomers to Boost ROS Generation for Photodynamic Therapy
Jiahui Cui, Yixuan Bao, Yinghui Lv, Chaohui Liang, Jianing Yuan, Shujing Liu, Xinyu Wang, Yifei Gao, Chen Zhang, Jinfeng Chen, Yongqian Zhang, Minggang Tian, Chao Chen, Ruoyao ZhangABSTRACT
Photodynamic therapy (PDT) has become a burgeoning alternative modality in clinics to treat cancer, and photosensitizers are the critical components for PDT. Herein, considering that the radiative transition from the S 1 to S 0 energy states in H ‐aggregates is symmetry‐forbidden, we proposed that H ‐aggregates were more prone to undergo intersystem crossing (ISC), thereby generating a photodynamic effect. Based on this hypothesis, we have successfully designed and synthesized a pair of isomers with planar structure, 2‐IVQ and 4‐IVQ, to seek for an efficient sensitizer working on H ‐aggregation mechanism. 2‐IVQ tends to form H ‐aggregates more readily, and the formation of H ‐aggregates at high concentrations actually enables effective generation of the photodynamic effect. Interestingly, at low concentrations, 2‐IVQ exhibits a weaker photodynamic effect compared to 4‐IVQ, which further supports the formation of H ‐aggregates in 2‐IVQ at high concentrations. Concentrated in mitochondria of cancer cells, tightly H ‐aggregated 2‐IVQ showed faster ROS generation that induced cell apoptosis, and could self‐report entire PDT process by visualizing the dyeing position change from mitochondria to nucleolus. In addition, 2‐IVQ had a substantial antitumor effect in H460 tumor bearing mice. This work provides a new strategy to promote the ISC for constructing effective phototheranostic reagents based on H ‐aggregation mechanism.