Zwitterionic polymers, containing both anionic and cationic groups in the sidechains, have received increasing attention over the past decade for biomedical application. Zwitterionic polymers are used in antifouling coatings, chaperon mimics to stabilize proteins, or as drug delivery vehicles, among others. In context of the latter aspect, we report the assembly of pH-responsive polymer lipid hybrid vesicles (HVs) using the amphiphilic block copolymer poly(cholesteryl methacrylate)-block-poly(2-methacryloyloxyethyl phosphorylcholine) (P1) as building block i.e., the hydrophilic extension representing the zwitterionic material. Three different lipids namely 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) were used to co-assemble with P1. Either the rehydration method or the electroformation method was used to obtain small HVs (sHVs) and giant HVs, respectively. Transmission electron microscopy images and fluorescent microscopy images revealed that the morphology of the assemblies depended on the type of lipid used as well as the polymer to lipid ratio. Förster resonance energy transfer experiments confirmed the presence of P1 and lipids in the same assembly. The membrane fluidity was analyzed using Laurdan as bilayer probe, showing low general polarization values for all types of sHVs, independently the type of lipid used compared to pristine vesicles. Carboxyfluorescein quenching assays demonstrated that sHVs had a slower release rate of the cargo compared to liposomes suggesting that the incorporation of P1 lowered the membrane permeability. The sHVs showed better structural stability when the pH was reduced compared to pH-responsive liposomes. Complementarily, sHVs were let to interact with giant liposomes as a simple model for cell membranes as a first step towards using this type of assemblies as drug carrier or scaffolds for artificial organelles.

Zwitterionic polymer-lipid hybrid vesicles

ACS Spring 2022

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