Real-time monitoring of etoposide prodrug activated by hydrogen peroxide with improved safety

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Vol. 7; no. 47; pp. 7548 - 7557
• Main Authors: Zhu, Jiawen, Chen, Jingting, Song, Dongmei, Zhang, Wenda, Guo, Jianpeng, Cai, Guiping, Ren, Yuhao, Wan, Chengying, Kong, Lingyi, Yu, Wenying
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 21.12.2019
• Subjects: adverse effects; animal disease models; Aromatic compounds; borates; Cancer; chemistry; Chemotherapy; Coumarin; Danio rerio; Drug delivery systems; drug therapy; Etoposide; Fluorescence; Hydrogen peroxide; monitoring; neoplasm cells; neoplasms; Real time; Safety; Side effects; Zebrafish
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/c9tb02041a

Etoposide is one of the most used first-line chemotherapeutic drugs. However, its application is still limited by its side effects. Herein, we designed a novel H 2 O 2 sensitive prodrug 6YT for selectively releasing the anti-cancer drug etoposide in cancer cells. In this paper, etoposide and a hydrogen peroxide (H 2 O 2 ) sensitive aryl borate ester group were linked by a fluorescent coumarin and finally the prodrug 6YT was generated. The fluorescence of coumarin was quenched before the connected aryl borate ester group was cleaved by H 2 O 2 . However, in the high level H 2 O 2 environment of the tumor, the fluorescence could be activated simultaneously with the release of etoposide, and the drug release state of the prodrug was monitored real-time. With the support of 6YT , we obtained direct and visual evidence of etoposide release in a high H 2 O 2 environment both in cells and zebrafish. The prodrug 6YT was also verified with comparable activity and improved safety with etoposide both in cells and in a mouse model. As a safe and effective prodrug, 6YT is expected to be one of the promising candidates in chemotherapy against cancer. A novel H 2 O 2 sensitive prodrug designed for selectively releasing etoposide in cancer cells with fluorescence monitoring and improved safety.