Intracellular enzyme-activatable prodrug for real-time monitoring of chlorambucil delivery and imaging  

作　　者：Meng Ni Wen-Jun Zeng Xin Xie Ze-Lin Chen Hao Wu Chang-Min Yu Bo-Wen Li 

机构地区：[1]College of Materials Science & Engineering South China University of Technology, C, uangzhou 510640, China

出　　处：《Chinese Chemical Letters》2017年第6期1345-1351,共7页中国化学快报（英文版）

基　　金：financial support by the Science and Technology Planning Project of Guangzhou(No.201607020015);the Science and Technology Planning Project of Guangdong Province(No.2014A010105009)

摘　　要：Carboxylesterase,a necessary enzyme in various mammalian cells,has been employed in various biological applications.Herein,we designed and synthesized a novel carboxylesterase-based prodrug,which can realize simultaneous drug-release imaging and cancer chemotherapy.This prodrug comprises three parts：coumarin as the fluorophore and the cleavable architecture,chlorambucil as the anticancer drug,and acetyl group as the enzyme-responsive unit.The presence of carboxylesterase leads to the activation of coumarin fluorescence,and this fluorescence serves as the reporting signal for assessing the enzyme level and drug release.Moreover,the prodrug was incorporated in liposome for monitoring drug release and chemotherapeutic effect in living cells.Upon internalization by HeLa cells,the prodrug can release chlorambucil and exhibit high cytotoxicity.This approach may provide some helpful insights for enhancing therapeutic effect and tracking the release of prodrug.Carboxylesterase,a necessary enzyme in various mammalian cells,has been employed in various biological applications.Herein,we designed and synthesized a novel carboxylesterase-based prodrug,which can realize simultaneous drug-release imaging and cancer chemotherapy.This prodrug comprises three parts：coumarin as the fluorophore and the cleavable architecture,chlorambucil as the anticancer drug,and acetyl group as the enzyme-responsive unit.The presence of carboxylesterase leads to the activation of coumarin fluorescence,and this fluorescence serves as the reporting signal for assessing the enzyme level and drug release.Moreover,the prodrug was incorporated in liposome for monitoring drug release and chemotherapeutic effect in living cells.Upon internalization by HeLa cells,the prodrug can release chlorambucil and exhibit high cytotoxicity.This approach may provide some helpful insights for enhancing therapeutic effect and tracking the release of prodrug.

关 键 词：Prodrug Carboxylesterase Chlorambucil Fluorescent imaging Liposomes 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]