Controlling Morphologies of Redox-Responsive Polymeric Nanocarriers for a Smart Drug Delivery System

Redox-responsive nanocarriers using disulfides or thiols have received considerable attention owing to the higher levels of glutathione (GSH) in cancer cells than those in extracellular fluids. Nevertheless, the normal-to-cancer-cell selectivity of these nanocarriers has not yet been clarified. Nanocarriers exhibit different cytotoxicities depending on the morphologies they adopt under the redox-active conditions typically existing in cancerous cells. Therefore, not only GSH levels but also reactive oxygen species (ROS) levels and other complex cancerous cell conditions must be considered for the development of smart drug delivery systems. In this article, we review the structural design of redox-responsive polymers that exhibit different morphological changes in environments akin to cancerous cells (e. g., GSH- and ROS-abundant conditions). In addition, we propose a molecular design for the spatiotemporal control of nanocarrier morphology depending on the levels of both GSH and ROS upon photoirradiation to increase the cytotoxicity difference between normal and cancer cells.