ROS activated prodrug for ALDH overexpressed cancer stem cells.

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.