北京大学张俊龙团队报道了光动力疗法中克服光毒性效应的seco-Chlorin光敏剂的生物仿生设计。相关研究成果发表在2022年4月20日出版的国际学术期刊《德国应用化学》。

光动力疗法（PDT）是一种针对一系列癌症和非恶性疾病的非侵入性治疗方式，但必须注意治疗后引起光毒性反应的风险。

该文中，研究人员报告一种新一代光敏剂（PSs）的仿生设计，它不仅能有效产生活性氧，而且在治疗后能快速代谢，以克服不良副作用。研究人员构建了一系列的b-吡咯开环二氯吡啶，称为贝达菲（BP）、贝达菲内酯（BPL）及其锌（II）衍生物（ZnBP和ZnBPL），具有强烈的近红外吸收和高效的O₂光敏作用。

根据包括时间分辨吸收、动力学和同位素标记在内的机理研究显示，ZnBPL的辐照通过原位生成的O₂而不是1O₂，产生了非细胞毒性、可代谢的苯达菲乙酰胺（ZnBPD）。此外，水溶性ZnBPL显示出有效的治疗效果、快速的代谢和可忽略的光毒性反应。

附：英文原文

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

Author: Jun-Long Zhang, 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

Issue&Volume: 2022-04-20

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  b  -pyrrolic ring-opening secochlorins, 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.

DOI: 10.1002/anie.202204330

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202204330