Composition-dependent tunability of the cell interactions of hybrid lipid – block copolymer vesicles

Hybrid vesicles composed of phospholipids and block copolymers are of interest for a wide range of applications due to the broad tunability of their material properties that can synergistically combine desirable properties of liposomes and polymersomes. A major application of vesicles in biotechnology has been in the field of drug delivery, where understanding and controlling vesicle interactions with cells is of vital importance. Here, we investigate the tunability of hybrid vesicle interaction with three distinct cell lines through modulating non-specific interactions. We formulate vesicles composed of three different constituents, the zwitterionic lipid 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the amphiphilic diblock copolymer Poly(1,2-butadiene)-b-poly(ethylene oxide) (PBD₂₂-PEO₁₄). This enables the tunability of cell interactions through electrostatic attraction to anionic cellular membranes and steric repulsion from the polymeric PEO brush layer. We establish a microfluidic flow protocol to enhance the reproducibility of vesicle-cell interactions by controlling the hydrodynamic stresses during incubation and washing steps. We demonstrate a high degree of tunability of cell interactions and low cytotoxicity across the three cell lines investigated (HFFF2, HEK293, HepG2). These initial findings offer critical insights into the engineering of hybrid vesicles and their potential applications in drug delivery.