Stabilization of Peptide-Based Vesicles via in situ Oxygen-Mediated Cross-Linking

Reversible vesicles from poly(L-glutamic acid)65-block-poly[(L-lysine)-ran-(L-3,4-dihydroxyphenylalanine)]75 [PLGA65-b-P(LL-r-DOPA)75] block copolypeptide adopt different configurations depending on the surrounding pH. At pH?=?3, AFM and TEM images show ellipsoidal morphologies, whereas at pH?=?12 both TEM and AFM reveal the formation of hollow vesicles. At pH?=?12, the P(LL-r-DOPA) block forms the internal layer of the vesicle shell and the subsequent oxygen-mediated oxidation of the phenolic groups of the DOPA lead to the formation of quinonic intermediates, which undergo intermolecular dimerization to stabilize the vesicles via in situ cross-linking. Consequently, the vesicles maintain their shape even when the pH is reversed back to 3, as confirmed by AFM and TEM.