One-pot synthesis of reactive oxygen species (ROS)-self-immolative polyoxalate prodrug nanoparticles for hormone dependent cancer therapy with minimized side effects
Literature Information
Anita Höcherl, Eliézer Jäger, Alessandro Jäger, Martin Hrubý, Rafał Konefał, Olga Janoušková, Jiří Spěváček, Yaming Jiang, Peter W. Schmidt, Timothy P. Lodge, Petr Štěpánek
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.
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