Reactive oxygen species and glutathione dual redox-responsive micelles for selective cytotoxicity of cancer.

Abstract

This study developed reactive oxygen species (ROS) and glutathione (GSH) dual redox-responsive micelles, which encapsulate anticancer drug camptothecin (CPT), protect CPT activity, and trigger CPT release in cancer cell H2O2- or GSH-rich surroundings. Experimental results show that CPT-loaded dual redox-responsive micelles remain stable at low levels of ROS and GSH in blood circulation, have high redox sensitivities needed to CPT release in cancer cells with high ROS or GSH (e.g., lung, gastric, and colon cancer cells), and prevent undersigned CPT toxicity in ROS/GSH balanced normal cells (e.g., fibroblast cells, etc.) or normal organs (e.g., liver, kidney, etc.). The CPT-loaded dual redox-responsive micelles also had high in vivo antitumor efficacy. This study demonstrates that ROS and GSH dual redox-responsive micelles have potential use as anticancer therapeutic nanomedicine in various cancer therapies.