ROS 激活前药用于 ALDH 过表达的癌症干细胞。

ROS activated prodrug for ALDH overexpressed cancer stem cells.

机构信息

Department of Chemistry, Korea University, Seoul 02841, Korea.

出版信息

Chem Commun (Camb). 2021 Dec 21;58(1):72-75. doi: 10.1039/d1cc05573a.

Abstract

Aldehyde dehydrogenase (ALDH), a cancer stem cell biomarker, is related to drug resistance. Co-treatment of anti-cancer drug (CPT) and ALDH inhibitor (DEAB) can overcome the drug resistance of cancer stem cells (CSCs) and finally cure cancers without relapse. We herein introduce a prodrug (DE-CPT) - consisting of 1,3-oxathiolane as an ROS responsive scaffold, and an aldehyde protecting group of DEAB - to deliver the CPT and DEAB upon reaction with ROS. From tests of the sphere-forming ability and CSC marker subpopulation, we found that DE-CPT efficiently decreases the CSCs population and kills the cancer cells.

摘要

醛脱氢酶（ALDH）是一种癌症干细胞标志物，与耐药性有关。联合使用抗癌药物（CPT）和 ALDH 抑制剂（DEAB）可以克服癌症干细胞（CSC）的耐药性，最终治愈癌症而不复发。我们在此介绍一种前药（DE-CPT）-由 1,3-氧硫杂环戊烷作为 ROS 响应支架和 DEAB 的醛保护基团组成-在与 ROS 反应时输送 CPT 和 DEAB。通过球体形成能力和 CSC 标志物亚群的测试，我们发现 DE-CPT 可有效降低 CSCs 群体并杀死癌细胞。