蛋白质水解
胶束
体内
PEG比率
化学
生物利用度
药理学
癌症研究
生物化学
医学
生物
水溶液
生物技术
物理化学
经济
酶
财务
作者
Junhui Ma,Lei Fang,Ziyong Sun,Meijing Li,Ting Fan,Guangya Xiang,Xiang Ma
标识
DOI:10.1002/adhm.202400109
摘要
Proteolysis targeting chimeras (PROTACs) technology has been rapidly developed as a novel and selective medicinal strategy for the degradation of cellular proteins in cancer therapy. However, the applications of PROTACs as the heterobifunctional molecules are largely limited by high molecular weight, low bioavailability, poor permeability, insufficient targeting and low efficacy in vivo. Herein, self-assembling micelles of FA-PEG-PROTAC are designed for cancer cell selective targeting and reductive-response proteolysis in tumor-bearing mice. FA-PEG-PROTAC are prepared by conjugating folic acid (FA)-PEG with EGFR-targeting PROTAC (PRO) via a disulfide bond. The FA-PEG-PROTAC micelles, formed by self-assembling, is demonstrated to significantly improve tumor targeting efficacy and exhibit excellent anti-tumor efficacy in mouse xenograft model compared to the traditional PROTACs. The strategy of applying self-assembled FA-PEG-PROTAC micelles in tumor therapy can not only improve targeted proteolysis efficiency but broaden applications in the development of PROTAC-based drugs. This article is protected by copyright. All rights reserved.
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