Biodegradable multiblock polyurethane micelles with tunable reduction-sensitivity for on-demand intracellular drug delivery

Redox-responsive nanovehicles containing disulfide bonds are particularly promising for targeted intracellular drug delivery. However, conventional reduction-sensitive nanocarriers generally lack control of stimuli-responsiveness due to their poor structural tunability. In this study, we developed a class of biodegradable multiblock polyurethanes bearing varied amounts of disulfide linkages in their backbone. The reducible polyurethanes exhibit interesting phase behavior and self-assembly properties, as well as triggered release profiles under an intracellular reduction-mimicking environment. It was found that the redox-sensitive polyurethane micelles can rapidly enter tumor cells and efficiently transport the encapsulated payloads into the cytosol. In vitro cytotoxicity studies demonstrated that the paclitaxel-loaded polyurethane micelles could inhibit the proliferation of tumor cells effectively, with the inhibition effects controlled by adjusting the disulfide content in the polymeric backbone. In addition, the drug-free nanomicelles possess good cytocompatibility toward both cancer cells and healthy cells. These multiblock bioresponsive polyurethanes hold great promise in the further development of controllable intracellular drug transporters.