(622d) Modified Oxalate-Based Doxorubicin (OX-Dox) Prodrugs for Reactive Oxygen Species (ROS)-Responsive Drug Release

Nanoparticle (NP)-mediated cancer therapeutics have been widely pursued to develop safer and more effective modalities. Although they have made tremendous progress in the fight against cancer, sustained drug release during systemic circulation and controlled release at the tumor site remain as the major challenges. These challenges can be addressed by a controlled release mechanism triggered by internal or external stimuli such as pH, enzyme, reactive oxygen species (ROS), light, ultrasound, and irradiation. Because the ROS level in the cancer cells is much higher than the healthy ones, ROS can be used as an effective stimulus to trigger the drug release.

Here, we developed a few different modified oxalate-based Dox (OX-Dox) prodrugs. After confirming the successful synthesis of these prodrugs using MS and ¹H NMR, their release kinetics was studied using different concentrations of H₂O₂ and HRP. Then the MDA-MB-231 and MDA-MB-468 cell lines were chosen to compare and evaluate the efficacy of the synthesized OX-Dox prodrugs using the MTS and clonogenic assays. Also, fluorescent imaging and flow cytometry were employed to compare the in vitro cellular uptake of these different OX-Dox prodrugs.