ROS and GSH Dual‐Responsive GEM Prodrug Micelles for ROS‐Triggered Fluorescence Turn on Bioimaging and Cancer Therapy

Abstract Nanocarriers with minimal drug leakage in blood and sufficient drug release at tumor sites are essential for tumor targeted drug delivery and bioimaging. Herein, a reactive oxygen species (ROS) and glutathione (GSH) dual‐responsive aggregation‐induced quenching (ACQ) prodrug micelle system is developed based on PMPC‐P (Se‐ co ‐RB)‐P (SS‐GEM) copolymer to avoid drug leakage and specifically locate the tumor via a ROS‐triggered fluorescence turn on manner. Selenium (Se) group is designed to respond to the ROS environment of tumor so as to turn on the fluorescence of Rhodamine B (RB) and Gemcitabine (GEM) is conjugated to the copolymer via a disulfide bond. These GEM prodrug micelles exhibit small particle size of 166.3 nm with uniformed size distribution, a very weak fluorescence emission, and minimal drug release with only 3.33% drug release under physiological conditions after 48 h. However, ROS (0.1% H 2 O 2 ) and GSH (10 × 10 −3 m ) could synergistically promote disassembly of the micellar structure which causes accelerated drug release up to around 91.57% after 48 h. These prodrug micelles exhibit great in vitro and in vivo antitumor ability with minimal side effects. This novel drug delivery system provides new possibilities for designing stimuli‐responsive nanocarriers for tumor therapy and bioimaging.