Overproduction of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), superoxide anion radical, and the hydroxyl radical, is observed in may types of cancer, which induces oxidative stress in the tumor microenvironment. This characteristic oxidative microenvironment is the hallmark of cancer and provides a unique opportunity for cancer-specific drug delivery. In the field of drug delivery research, a wide variety of oxidation-sensitive drug delivery systems that release drugs in response to ROS have been developed to achieve cancer-targed drug delivery. Those include polymeric micelles and polymersomes that react with ROS and dissociate upon oxidation by ROS. So far, the majority of research focusses on improving oxidation sensitivity thereby enhancing drug release in cancer cells. However, drug carriers with high oxidation sensitiven also release non-negligible amount of drug in normal cells, which generate ROS at basal levels (generally 1-10% relative to cancer cells). Therefore, fine-tuning of the ROS sensitivity of drug carriers is essential for achieving cancer-specific drug delivery. In this presentation, we report desing, synthesis and characterization of polymeric micelles containing different thioether groups with varying oxidation sensitivities. The oxidation-sensitive dissociation of polymeric micelles containing different thioether groups was evaluated in the presence of H2O2 as well as in human liver cancer cells (HepG2) and human umbilical vein endothelial cells (HUVECs). Furthermore, the cytotoxicity assay was performed for the micelles loaded with doxorubicin in cancer and normal cells to demonstrate the potential applications in cancer chemotherapy.

Oxidation-sensitive thioether-containing polymeric micelles for cancer-targeted drug delivery

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ACS Fall 2022

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