Triggered Inversion of Dual Responsive Diblock Copolypeptide Vesicles
Casey A. Morrison, Ethan P. Chan, Timothy J. Deming
Abstract
High Resolution Image Download MS PowerPoint Slide We report the synthesis of amphiphilic poly( l -methionine sulfoxide) x - b -poly(dehydroalanine) y, diblock copolypeptides, M O x A DH y, and their self-assembly into submicrometer-diameter unilamellar vesicles in aqueous media. The formation of vesicles was observed over an unprecedented range of copolypeptide compositions due to the unique properties and chain conformations of A DH hydrophobic segments. These copolypeptides incorporate two distinct thiol reactive components where each segment can respond differently to a single thiol stimulus. Incubation of M O 35 A DH 30 vesicles with glutathione under intracellular mimetic conditions resulted in vesicle disruption and release of cargo. Further, incubation of M O 35 A DH 30 vesicles with thiolglycolic acid resulted in a reversal of amphipilicity and successful in situ inversion of the vesicle assemblies. This conversion of biomimetic polymer vesicles into stable inverted vesicles using a biologically relevant stimulus at physiological pH and temperature is unprecedented. These results provide insights toward the development of advanced functional synthetic assemblies with potential uses in biology and medicine.