Influence of Polymer Structure and Architecture on Drug Loading and Redox-Triggered Release

Disulfide cross-linked nanoassemblies have attracted considerable attention as a drug delivery vehicle due to their responsiveness to the natural redox gradient in biology. Fundamentally understanding the factors that influence the drug loading capacity, encapsulation stability, and precise control of the liberation of encapsulated cargo would be profoundly beneficial to redox-responsive materials. Reported herein are block copolymer (BCP)-based self-cross-linked nanogels, which exhibit high drug loading capacity, high encapsulation stability, and controllable release kinetics. BCP nanogels show considerably higher loading capacity and better encapsulation stability than the random copolymer nanogels at micromolar glutathione concentrations. By partially substituting thiol-reactive pyridyl disulfide into the unreactive benzyl or butyl group, we observed opposite effects on the cross-linking process of BCP nanogels. We further studied the redox-responsive cytotoxicity of our drug-encapsulated nanogels in various cancer cell lines.

Automated summary

Disulfide cross-linked nanoassemblies have shown great potential as drug delivery vehicles due to their responsiveness to the natural redox gradient in biology. This study focused on block copolymer-based self-cross-linked nanogels, which exhibited high drug loading capacity, encapsulation stability, and controllable release kinetics. By partially substituting thiol-reactive compounds into unreactive groups, opposite effects on the cross-linking process of the nanogels were observed. In addition, the redox-responsive cytotoxicity of the drug-encapsulated nanogels in various cancer cell lines was further studied.