Low-Dose X-ray-Responsive Diselenide Nanocarriers for Effective Delivery of Anticancer Agents

X-ray-responsive nanocarriers for anticancer drug delivery have shown great promise for enhancing the efficacy of chemoradiotherapy. A critical challenge remains for development of such radiation-controlled drug delivery systems (DDSs), which is to minimize the required X-ray dose for triggering the cargo release. Herein, we design and fabricate an effective DDS based on diselenide block copolymers (as nanocarrier), which can be triggered to release their cargo with a reduced radiation dose of 2 Gy due to their sensitivity to both X-ray and the high level of reactive oxygen species (ROS) in the microenvironment of cancer cells. The underlying molecular mechanism is further illustrated by proton nuclear magnetic resonance (H-1 NMR) experiments and density functional theory (DFT) calculations. In vivo experiments on tumor-bearing mice validated that the loaded drugs are effectively delivered to the tumor site and exert remarkable antitumor effects (minimum tumor volume/weight) along with X-ray. Furthermore, the diselenide nanocarriers exhibit no noticeable cytotoxicity. These findings provide new insights for the de novo design of radiation-controlled DDSs for cancer chemoradiotherapy.