Synthesis of a Reactive Oxygen Species-Responsive Doxorubicin Derivative

A heterobifunctional reactive oxygen species (ROS)-responsive linker for directed drug assembly onto and delivery from a quantum dot (QD) nanoparticle carrier was synthesized and coupled to doxorubicin using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC)/sulfo-NHS coupling. The doxorubicin conjugate was characterized using H-1 NMR and LC-MS and subsequently reacted under conditions of ROS formation (Cu2+/H2O2) resulting in successful and rapid thioacetal oxidative cleavage, which was monitored using H-1 NMR.