| Title | Radiotherapy-Induced Cleavage of Quaternary Ammonium Groups Activates Prodrugs in Tumors |
| Authors | Guo, Zhibin Hong, Hanyu Zheng, Yuedan Wang, Ziyang Ding, Zexuan Fu, Qunfeng Liu, Zhibo |
| Affiliation | Peking Univ, Radiochem & Radiat Chem Key Lab Fundamental Sci, NMPA Key Lab Res & Evaluat Radiopharmaceut,Beijin, Key Lab Bioorgan Chem & Mol Engn,Minist Educ,Coll, Beijing 100871, Peoples R China Peking Univ, Tsinghua Univ, Ctr Life Sci, Beijing 100871, Peoples R China |
| Keywords | CLICK CHEMISTRY CHEMOTHERAPY TERTIARY AMINES CANCER DRUGS |
| Issue Date | Jul-2022 |
| Publisher | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION |
| Abstract | Cleavage chemistry offers a new chance to activate chemotherapeutic prodrugs in a tumor-selective manner, yet developing spatiotemporally controllable cleavage chemistry with deep tissue penetration is still a great challenge. Herein, we present a novel radiotherapy-triggered cleavage chemistry that enables controlled drug release in tumors. Quaternary ammonium groups are identified as masking groups that can be efficiently removed by hydrated electrons (e(aq)(-)) from water radiolysis. The subsequently released tertiary amines can be anti-cancer toxins or readily release functional molecules via 1,6-elimination. This radiotherapy-induced cleavage works successfully in living cells and tumor-bearing mice, showing remarkable treatment efficacy when the mice are given carfilzomib prodrug and radiotherapy. This strategy provides a new perspective for combinational radiochemotherapy, which is the first-line treatment for over 50 % of cancer patients. |
| URI | http://hdl.handle.net/20.500.11897/648975 |
| ISSN | 1433-7851 |
| DOI | 10.1002/anie.202205014 |
| Indexed | EI SCI(E) |
| Appears in Collections: | å å¦ä¸ å å å·¥ç¨ å¦é ¢ 生物有机与分子工程教育部重点实验室 生命科学学院 |
