Abstract The aim of the present study is to investigate the interactions between liposomes and proteins and to evaluate the role of liposomal lipid composition and concentration in the formation of protein corona. Liposomes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or hydrogenated soybean phosphatidylcholine (HSPC) with 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (sodium salt) (DPPG), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000] (DPPE-PEG 3000), cholesterol (CH) or mixtures of these lipids, were prepared at different concentrations by the thin-film hydration method. After liposomes were dispersed in HPLC-grade water and foetal bovine serum (FBS), their physicochemical characteristics, such as size, size distribution, and ζ-potential, were determined using dynamic and electrophoretic light scattering. Aggregation of DPPC, HSPC, DPPC:CH (9:1 molar ratio), and HSPC:CH (9:1 molar ratio) in FBS was observed. On the contrary, liposomes incorporating DPPG lipids and CH both in a molar ratio of 11% were found to be stable over time, while their size did not alter dramatically in biological medium. Liposomes containing CH and PEGylated lipids retain their size in the presence of serum as well as their physical stability. In addition, our results indicate that the protein binding depends on the presence of polyethylene glycol (PEG), CH, concentration and surface charge. In this paper, we introduce a new parameter, fraction of stealthiness (Fs), for investigating the extent of protein binding to liposomes. This parameter depends on the changes in size of liposomes after serum incubation, while liposomes have stealth properties when Fs is close to 1. Thus, we conclude that lipid composition and concentration affect the adsorption of proteins and the liposomal stabilization.

中文翻译：

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蛋白质-脂质体相互作用的物理化学研究：脂质体组成和浓度对蛋白质结合的影响

摘要 本研究的目的是研究脂质体与蛋白质之间的相互作用，并评估脂质体脂质组成和浓度在蛋白质冠形成中的作用。由 1,2-二棕榈酰-sn-甘油-3-磷酸胆碱 (DPPC) 或氢化大豆磷脂酰胆碱 (HSPC) 与 1,2-二棕榈酰-sn-甘油-3-磷酸-(1'-rac-甘油) 组成的脂质体 (钠盐) (DPPG)、1,2-二棕榈酰-sn-甘油-3-磷酸乙醇胺-N-[甲氧基(聚乙二醇)-3000] (DPPE-PEG 3000)、胆固醇 (CH) 或这些脂质的混合物，是不同浓度的薄膜水合法制备。脂质体分散在 HPLC 级水和胎牛血清 (FBS) 中后，它们的理化特性，如大小、大小分布和 ζ 电位，使用动态和电泳光散射测定。观察到 DPPC、HSPC、DPPC:CH（9:1 摩尔比）和 HSPC:CH（9:1 摩尔比）在 FBS 中的聚集。相反，发现以 11% 的摩尔比掺入 DPPG 脂质和 CH 的脂质体随着时间的推移是稳定的，而它们的大小在生物介质中没有显着变化。含有 CH 和聚乙二醇化脂质的脂质体在血清存在的情况下保持其大小及其物理稳定性。此外，我们的结果表明蛋白质结合取决于聚乙二醇 (PEG)、CH、浓度和表面电荷的存在。在本文中，我们引入了一个新参数，即隐身分数 (Fs)，用于研究蛋白质与脂质体的结合程度。该参数取决于血清孵育后脂质体大小的变化，