Triggered Inversionof Dual Responsive Diblock CopolypeptideVesicles

We report the synthesis of amphiphilic poly(l-methionine sulfoxide)_<i>x</i>-<i>b</i>-poly(dehydroalanine)_<i>y</i>, diblock copolypeptides, <b>M</b>^<b>O</b>_<i>x</i><b>A</b>^<b>DH</b>_<i>y</i>, 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 <b>A</b>^<b>DH</b> hydrophobic segments. These copolypeptides incorporate two distinct thiol reactive components where each segment can respond differently to a single thiol stimulus. Incubation of <b>M</b>^<b>O</b>_<b>35</b><b>A</b>^<b>DH</b>_<b>30</b> vesicles with glutathione under intracellular mimetic conditions resulted in vesicle disruption and release of cargo. Further, incubation of <b>M</b>^<b>O</b>_<b>35</b><b>A</b>^<b>DH</b>_<b>30</b> vesicles with thiolglycolic acid resulted in a reversal of amphipilicity and successful <i>in situ</i> 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.