Fabrication of polymersomes with liposome-extracted lipid membrane preserving original leaflet asymmetry

Utilizing biological membranes, such as red blood cells and extracellular vesicles, to create bio-camouflaged carriers presents a promising strategy for biomedical applications and drug delivery systems to evade the immune system and reach specifically targeted organs. In this report, as a preliminary study in carrier preparation, we aimed to transplant a lipid membrane from a general liposome-a model of a natural cell membrane-into a peptide vesicle composed of amphiphilic polydepsipeptides. Consequently, we successfully produced a peptide-lipid hybrid vesicle (PLHV) that consisted of phase-separated lipid and peptide membranes, exhibiting a diameter of 50-90 nm. The preparation method for the PLHV involved three simple steps: (1) preparing the liposome, (2) adding the amphiphilic polydepsipeptide, poly(Sar)₃₂-(L-Leu-Aib)₇ (SL14), to the liposome dispersion, and (3) applying heat treatment at 90 °C for 1 hour. Emission quenching tests of NBD tethered to the membrane surface and FRET analysis indicated that the PLHV included an independent lipid domain distinct from the peptide domain, preserving the membrane asymmetry of the original liposome within this lipid domain. Although hybrid vesicles and liposomes had similar encapsulation efficiency, hybrid vesicles showed greater storage stability due to the rigidity of the peptide domain. This technology illuminates the development of drug delivery systems utilizing natural cell membranes.