On the assembly of zwitterionic block copolymers with phospholipids

Materials containing zwitterionic polymers are interesting candidates for diverse applications due to their ver-satile properties. The assembly of the amphiphilic block copolymer poly(cholesteryl methacrylate)-block-poly(2-methacryloyloxyethyl phosphorylcholine) with three different phospholipids (1,2-dioleoyl-sn-glycero-3-phos-phocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) and 1,2-dioleoyl-sn-glycero-3-phos-phoethanolamine (DOPE)) into small and giant vesicles is reported focusing on their morphology, size, and membrane properties. Giant hybrid vesicles were obtained for all types of lipids, but DOPC was more suitable to assemble small hybrid vesicles without a large fraction of hybrid micelles present. Further, the permeability of the small vesicle membranes towards 5(6)-carboxyfluorescein is very similar to comparable sized liposomes. In contrast, the permeability of the giant hybrid vesicle membranes towards 5(6)-carboxy-X-rhodamine is higher compared to only cholesterol-containing lipid giant vesicles. DOPS-containing vesicles showed pH-dependent morphology changes. Hybrid vesicles containing DOPS and DOPE in addition to the block copolymer have the highest association with HepG2 cells. In contrast, only DOPC-containing hybrid vesicles can be incorporated into alginate beads. Taken together, using these block copolymer with a zwitterionic hydrophilic extension of the chosen architecture offers fundamental insight into the possibility to assemble hybrid vesicles and their potential in bottom-up synthetic biology.