Acid-sensitive PEGylated cabazitaxel prodrugs for antitumor therapy  

作　　者：Tao Liu Hui Zou Jingqing Mu Na Yu Yang Xu Guohua Liu Xingjie Liang Shutao Guo 

机构地区：[1]Key Laboratory of Functional Polymer Materials of Ministry of Education,State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer Chemistry,College of Chemistry,Nankai University,Tianjin 300071,China [2]Laboratory of Controllable Nanopharmaceuticals,CAS Center for Excellence in Nanoscience,CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety,National Center for Nanoscience and Technology,Beijing 100190,China [3]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Chinese Chemical Letters》2021年第5期1751-1754,共4页中国化学快报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.51773098);the Natural Science Foundation of Tianjin of China(No.18JCYBJC28300);the Fundamental Research Funds for Central Universities(China).

摘　　要：Although the antitumor drug cabazitaxel shows great therapeutic potential,its high toxicity and poor water solubility limit its utility.However,the use of stimuli-responsive prodrugs is a promising strategy for overcoming these limitations.Herein,we report the synthesis of two highly water soluble,acidsensitive PEGylated acyclic-ketal-linked cabazitaxel prodrugs(PKCs)with improved antitumor efficacy.In an acidic tumor microenvironment,the PKCs hydrolyzed rapidly to release the native drug,whereas they were stable in the normal physiological environment.Compared with cabazitaxel injection,the PKCs had much higher maximum tolerated doses:and in an MDA-MB-231 subcutaneous xenograft nude mouse model,the PKCs showed better antitumor efficacy and safety than cabazitaxel injection.The prodrug strategy reported herein could be useful for the development of other water soluble,acidsensitive prodrugs with improved efficacy.

关 键 词：PRODRUGS Acid-sensitive Antitumor therapy CABAZITAXEL PEGYLATION 

分 类 号：TQ460.1[化学工程—制药化工]