Martinez Juan, Ingram Nicola, Kapur Nikil, Jayne David G, Beales Paul A
School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, West Yorkshire LS2 9JT, UK; Leeds Institute for Medical Research, University of Leeds, Leeds, West Yorkshire LS9 7TF, UK.
Leeds Institute for Medical Research, University of Leeds, Leeds, West Yorkshire LS9 7TF, UK.
J Colloid Interface Sci. 2025 Sep 15;694:137664. doi: 10.1016/j.jcis.2025.137664. Epub 2025 Apr 21.
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) (PBD-PEO). 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.
由磷脂和嵌段共聚物组成的混合囊泡因其材料特性具有广泛的可调性而在广泛的应用中备受关注，这种可调性可以协同结合脂质体和聚合物囊泡的理想特性。囊泡在生物技术中的一个主要应用领域是药物递送，在该领域中，了解和控制囊泡与细胞的相互作用至关重要。在这里，我们通过调节非特异性相互作用来研究混合囊泡与三种不同细胞系相互作用的可调性。我们制备了由三种不同成分组成的囊泡，两性离子脂质1-棕榈酰-2-油酰甘油-3-磷酸胆碱（POPC）、阳离子脂质1,2-二油酰基-3-三甲基铵丙烷（DOTAP）和两亲性二嵌段共聚物聚（1,2-丁二烯）-b-聚（环氧乙烷）（PBD-PEO）。这使得通过对阴离子细胞膜的静电吸引和聚合物PEO刷层的空间排斥来调节细胞相互作用成为可能。我们建立了一种微流控流动方案，通过控制孵育和洗涤步骤中的流体动力应力来提高囊泡-细胞相互作用的重现性。我们证明了在所研究的三种细胞系（HFFF2、HEK293、HepG2）中，细胞相互作用具有高度的可调性且细胞毒性较低。这些初步发现为混合囊泡的工程设计及其在药物递送中的潜在应用提供了关键见解。
