A novel FAPa-basedZ-Gly-Pro epirubicin prodrug for improving tumor-targeting chemotherapy

作者：Wang, Jun; Li, Qiuwen; Li, Xiaojuan; Yuan, Weiqi; Huang, Sichao; Cai, Shaohui^*; Xu, Jun^*

来源：European Journal of Pharmacology, 2017, 815: 166-172.

DOI：10.1016/j.ejphar.2017.09.016

• Prodrug
• EPI
• Fibroblast activation protein-alpha (FAP alpha)
• Dipeptide (Z-Gly-Pro)
• Targeting
• Cardiotoxicity

Fibroblast activation protein-alpha (FAP alpha) 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 FAPa-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 FAPa and could exhibit similar antitumor effects as EPI in vitro in FAPa over-expressed tumor cells (4T1/FAP alpha(+)). Furthermore, the evaluation of antitumor activity of Z-GP-EPI in vivo was implemented in a 4T1/FAP alpha(+) tumor-bearing mice xenograft model. Our results illustrated that Z-GP-EPI had similar antitumor effects in 4T1/FAP alpha(+) tumor-bearing mice and showed no visible cardiotoxicity side effects compared with free EPI. Thus, our study indicated that this FAPa-activated prodrug targeting strategy may provide a new mechanism for the targeted delivery of antitumor agents and improve their safety levels.

• 出版日期2017-11-15
• 单位暨南大学