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.