Poly(Sitosterol)‐Based Hydrophobic Blocks in Amphiphilic Block Copolymers for the Assembly of Hybrid Vesicles

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2024-10, Vol.20 (40), p.e2401934-n/a
• Main Authors: Brodszkij, Edit, Ryberg, Cecilie, Lyons, Joseph A., Juhl, Dennis Wilkens, Nielsen, Niels Chr, Sigalas, Nikolaos I., Lyulin, Alexey V., Pedersen, Jan Skov, Städler, Brigitte
• Format: Article
• Language: English
• Subjects: Block copolymers; Copolymers; Diffusion barriers; Diffusion rate; Electroforming; Energy transfer; Fluorescent indicators; hybrid vesicles; Hydrophobicity; Lipids; Liposomes; Membranes; Phosphatidylcholine; Resonance scattering; Rhodamine; self‐assembly; Skewed distributions; Vesicles
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.202401934

Amphiphilic block copolymer and lipids can be assembled into hybrid vesicles (HVs), which are an alternative to liposomes and polymersomes. Block copolymers that have either poly(sitostryl methacrylate) or statistical copolymers of sitosteryl methacrylate and butyl methacrylate as the hydrophobic part and a poly(carboxyethyl acrylate) hydrophilic segment are synthesized and characterized. These block copolymers assemble into small HVs with soybean L‐α‐phosphatidylcholine (soyPC), confirmed by electron microscopy and small‐angle X‐ray scattering. The membrane's hybrid nature is illustrated by fluorescence resonance energy transfer between labeled building blocks. The membrane packing, derived from spectra when using Laurdan as an environmentally sensitive fluorescent probe, is comparable between small HVs and the corresponding liposomes with molecular sitosterol, although the former show indications of transmembrane asymmetry. Giant HVs with homogenous distribution of the block copolymers and soyPC in their membranes are assembled using the electroformation method. The lateral diffusion of both building blocks is slowed down in giant HVs with higher block copolymer content, but their permeability toward (6)‐carboxy‐X‐rhodamine is higher compared to giant vesicles made of soyPC and molecular sitosterol. This fundamental effort contributes to the rapidly expanding understanding of the integration of natural membrane constituents with designed synthetic compounds to form hybrid membranes. Amphiphilic block copolymers with a sitosteryl methacrylate‐based hydrophobic part and poly(carboxyethyl acrylate) for the hydrophilic segment are synthesized. These block copolymers, combined with soybean L‐α‐phosphatidylcholine, form small and giant hybrid vesicles with different properties compared to the corresponding liposomes with molecular sitosterol, advancing the understanding of integrating natural and synthetic compounds in hybrid membranes.