Tretiakova Daria, Kobanenko Maria, Le-Deygen Irina, Boldyrev Ivan, Kudryashova Elena, Onishchenko Natalia, Vodovozova Elena
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1/3, 119991 Moscow, Russia.
Membranes (Basel). 2022 Oct 23;12(11):1031. doi: 10.3390/membranes12111031.
Liposomes as drug carriers are usually injected into the systemic circulation where they are instantly exposed to plasma proteins. Liposome-protein interactions can affect both the stability of liposomes and the conformation of the associated protein leading to the altered biodistribution of the carrier. In this work, mutual effects of albumin and liposomal membrane in the course of the protein's adsorption were examined in terms of quantity of bound protein, its structure, liposome membrane permeability, and changes in physicochemical characteristics of the liposomes. Fluorescence spectroscopy methods and Fourier transform infrared spectroscopy (ATR-FTIR), which provides information about specific groups in lipids involved in interaction with the protein, were used to monitor adsorption of albumin with liposomes based on egg phosphatidylcholine with various additives of negatively charged lipidic components, such as phosphatidylinositol, ganglioside GM, or the acidic lipopeptide. Less than a dozen of the protein molecules were tightly bound to a liposome independently of bilayer composition, yet they had a detectable impact on the bilayer. Albumin conformational changes during adsorption were partially related to bilayer microhydrophobicity. Ganglioside GM showed preferable features for evading undesirable structural changes.
脂质体作为药物载体通常被注入体循环，在那里它们会立即暴露于血浆蛋白中。脂质体与蛋白的相互作用会影响脂质体的稳定性以及相关蛋白的构象，进而导致载体生物分布的改变。在这项工作中，从结合蛋白的量、其结构、脂质体膜通透性以及脂质体理化特性的变化等方面，研究了白蛋白与脂质体膜在蛋白吸附过程中的相互作用。利用荧光光谱法和傅里叶变换红外光谱法（衰减全反射傅里叶变换红外光谱法，ATR-FTIR）来监测白蛋白与基于鸡蛋磷脂酰胆碱并添加了各种带负电荷脂质成分（如磷脂酰肌醇、神经节苷脂GM或酸性脂肽）的脂质体的吸附情况，其中ATR-FTIR可提供与蛋白相互作用的脂质中特定基团的信息。无论双层膜组成如何，少于一打（约12个）的蛋白分子会紧密结合到脂质体上，但它们对双层膜有可检测到的影响。吸附过程中白蛋白的构象变化部分与双层膜的微疏水性有关。神经节苷脂GM在避免不良结构变化方面表现出较好的特性。
