Nanoscale Polyelectrolyte Complex Vesicles from Bioinspired Peptidomimetic Homopolymers with Zwitterionic Property and Extreme Stability

The complexation of polyelectrolytes ranging from biomacromolecules to synthetic polymers offers a great opportunity to construct a new generation of hierarchical materials. Here, we report a new type of nanoscale peptidomimetic polyelectrolyte complex vesicles (PCVs), with excellent aqueous stability over time and a wide range of pH, assembled from a pair of oppositely charged bioinspired homopolypeptoids and homopoly(2-oxazoline)s. This is distinct from the traditional homopolyelectrolytes that typically form microscale-sized liquid coacervates or solids. Through a systematic study, we demonstrated that the appropriate strength of hydrogen-bonding effects arising from the polar tertiary amide groups is significantly important for the formation of the vesicle. The prepared PCVs bearing water inner lumen are capable of encapsulating hydrophilic cargo molecules with good selectivity and tunable permeability, which can facilitate the diffusion of water-soluble therapeutic molecules, proteins, and enzymes. Due to the simultaneous surface display of positive and negative charges, the vesicles show excellent stability in physiological protein solutions and low toxicity, similar to known zwitterionic polymers. These superior properties combined with the facile preparation strategy suggest that the binary PCVs could be excellent drug delivery candidates for biomedical and engineering applications.