A novel FAPα-based Z-Gly-Pro epirubicin prodrug for improving tumor-targeting chemotherapy.

Fibroblast activation protein-α (FAPα) is a serine protease of the post-prolyl peptidase family that is specifically expressed in the majority of human epithelial tumors, but not in normal tissues. In this study, we demonstrated the anti-tumor activity of a novel targeting drug formed by conjugating epirubicin (EPI) with an FAPα-specific dipeptide (Z-Gly-Pro) and named it Z-GP-EPI. Consistent with this tumor-targeting delivery strategy, the results illustrated that Z-GP-EPI could release EPI efficiently after incubating with FAPα and could exhibit similar antitumor effects as EPI in vitro in FAPα over-expressed tumor cells (4T1/FAPα+). Furthermore, the evaluation of antitumor activity of Z-GP-EPI in vivo was implemented in a 4T1/FAPα+ tumor-bearing mice xenograft model. Our results illustrated that Z-GP-EPI had similar antitumor effects in 4T1/FAPα+ tumor-bearing mice and showed no visible cardiotoxicity side effects compared with free EPI. Thus, our study indicated that this FAPα-activated prodrug targeting strategy may provide a new mechanism for the targeted delivery of antitumor agents and improve their safety levels. Copyright © 2017. Published by Elsevier B.V.

Citation

Jun Wang, Qiuwen Li, Xiaojuan Li, Weiqi Yuan, Sichao Huang, Shaohui Cai, Jun Xu. A novel FAPα-based Z-Gly-Pro epirubicin prodrug for improving tumor-targeting chemotherapy. European journal of pharmacology. 2017 Nov 15;815:166-172

PMID: 28919026

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