One-pot synthesis of reactive oxygen species (ROS)-self-immolative polyoxalate prodrug nanoparticles for hormone dependent cancer therapy with minimized side effects

A new reactive oxygen species (ROS)-sensitive, self-immolative biodegradable polyoxalate prodrug based on the anticancer chemotherapeutic hormone analog diethylstilbestrol was synthesized via one-pot step-growth polymerization. The nanoparticles prepared from this prodrug undergo self-immolative degradation releasing the chemotherapeutic drug in ROS-rich environments, e.g., in cancer cells. This new ROS self-immolative polyprodrug backbone eliminates the need for a linker between polymer chain and drug, resulting in a more specific drug release and minimized toxic side effects to non-ROS-producing cells as proven by in vitro experiments. The strategy enables re-utilization of a successful chemotherapeutic agent that has been clinically under-utilized due to dose-related side effects.