Bioinspired Design of <i>seco</i>‐Chlorin Photosensitizers to Overcome Phototoxic Effects in Photodynamic Therapy
Mengliang Zhu, Hang Zhang, Guangliu Ran, Yuhang Yao, Zi‐Shu Yang, Yingying Ning, Yi Yu, Ruijing Zhang, Xin‐Xin Peng, Jiahui Wu, Zhifan Jiang, Wenkai Zhang, Bing‐Wu Wang, Song Gao, Jun‐Long Zhang
Abstract
Abstract Photodynamic therapy (PDT) is a non‐invasive treatment modality against a range of cancers and nonmalignant diseases, however one must be aware of the risk of causing phototoxic reactions after treatment. We herein report a bioinspired design of next‐generation photosensitizers (PSs) that not only effectively produce ROS but undergo fast metabolism after treatment to overcome undesirable side effects. We constructed a series of β‐pyrrolic ring‐opening seco ‐chlorins, termed beidaphyrin ( BP ), beidapholactone ( BPL ), and their zinc(II) derivatives ( ZnBP and ZnBPL ), featuring intense near‐infrared absorption and effective O 2 photosensitization. Irradiation of ZnBPL led to a non‐cytotoxic, metabolizable beidaphodiacetamide ( ZnBPD ) via in situ generated O 2 .− but not 1 O 2 , as revealed by mechanistic studies including time‐resolved absorption, kinetics, and isotope labeling. Furthermore, water‐soluble ZnBPL showed an effective therapeutic outcome, fast metabolism, and negligible phototoxic reactions.