Bioinspired Design of seco-Chlorin Photosensitizers to Overcome Phototoxic Effects in Photodynamic Therapy

作者：Zhu, Mengliang; Zhang, Hang; Ran, Guangliu; Yao, Yuhang; Yang, Zi-Shu; Ning, Yingying; Yu, Yi; Zhang, Ruijing; Peng, Xin-Xin; Wu, Jiahui; Jiang, Zhifan; Zhang, Wenkai; Wang, Bing-Wu; Gao, Song; Zhang, Jun-Long^*

来源：Angewandte Chemie - International Edition, 2022, 61(28): e202204330.

DOI：10.1002/anie.202204330

• Photodegradation
• Photodynamic Therapy
• Reactive Oxygen Species
• seco-Chlorin
• Tetrapyrrole

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 beta-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 O-1(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.

• 单位
  北京大学