ROS/pH dual-sensitive emodin-chlorambucil co-loaded micelles enhance anti-tumor effect through combining oxidative damage and chemotherapy

Abstract

The high level of reactive oxygen species (ROS) at the tumor site has been widely used in the tumor targeted delivery. However, the ROS stimulus-responsive vector itself is also a ROS consumer, and the consumption of endogenous ROS may not be sufficient to maintain sustained drug release. In this study, we designed and synthesized ROS/pH dual-sensitive polymer micelles for the co-delivery of emodin (EMD) and chlorambucil (CLB). The release of quinone methides (QM) can consume glutathione (GSH), on the one hand, it can enhance the chemotoxicity of phenylbutyrate nitrogen mustard, on the other hand, emodin can induce oxidative damage of tumor cells and maintain the sustained targeted release of drugs.

Keywords: Chlorambucil; Emodin; GSH consumption; Oxidative damage; ROS/pH dual-sensitive.