Creation of polymersomes with changes in the membrane structure via disulfide crosslinking under reductive conditions for controlled gradual cargo release

Abstract

The controlled release of cargo from carriers is a critical challenge in drug delivery. Polymersomes are capsule-like structures self-assembled from amphiphilic polymers that can function as carriers. Although the sudden release of cargo has been achieved by inducing the overall structural collapse of polymersomes, the gradual release of cargo, which is key for decreasing the number of drug-administration cycles, remains a challenge. Disulfide crosslinking is one of the candidates for controlling the releasing ability of polymersomes. However, such previous research only focused on strategies for oxidation of thiol to induce disulfide crosslinking under oxidative conditions, which missed the potential for the disulfide crosslinking under reductive conditions. Herein, we realize a new strategy that disulfide crosslinking can be induced under reductive conditions. Amphiphilic polymers with multiple disulfide bonds were newly synthesized, and they self-assembled into polymersomes that facilitate the gradual release of cargo in a reductive environment. The addition of glutathione facilitated the successive crosslinking of the disulfide bonds in the membranes, resulting in a rigidified membrane structure. The changes in the membrane rigidity influenced the permeability of the cargo in the polymersome, resulting in its controlled release. We expect that our study will expand molecular design strategies to control the membrane properties of polymersomes.