用脂质膜-固定化硅胶整体柱分析阳离子脂质与寡核苷酸的相互作用：高效液相色谱方法

IF 3.9 2区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Langmuir Pub Date : 2025-01-22 DOI:10.1021/acs.langmuir.4c03667

Junghu Lee, Noriko Yoshimoto, Hayato Takase, Nozomi Morishita Watanabe, Yukihiro Okamoto, Hiroshi Umakoshi

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引用次数: 0

摘要

了解脂质膜与核苷酸药物之间的相互作用对核酸治疗至关重要。尽管已有几种方法用于评估核苷酸-脂质膜相互作用，但这些相互作用可能很复杂；这种复杂性源于外部因素，如离子强度或温度，如何影响脂质膜的整体特性。在本研究中，我们制备了一种脂质膜固定化单片二氧化硅（LMiMS）柱，用于高效液相色谱（HPLC）分析，以了解脂质膜与核酸的相互作用。首先，分析了lmims柱膜的拉曼位移、zeta电位、流动性和极性，并将其与具有相同脂质成分的分散脂质体（未固定化）进行了比较。结果表明，该色谱柱可以有效地模拟脂质膜的温度依赖性，表明固定化脂质膜可以作为分散脂质体膜的模型。随后，采用高效液相色谱法分析脂质膜与寡核苷酸的相互作用。在不同温度和流动相盐浓度下，确定LMiMS柱与核酸模型（聚10、25和50mer dC）之间的保留因子k。结果表明，盐浓度和相态对膜相互作用的影响是显著的。对保留系数k的进一步分析表明，在相变温度以下，相互作用较弱，而在相变温度以上，相互作用较强。结果表明，膜的性能（刚度和极性）也与膜的相互作用有关，可以用LMiMS柱来评价。这种分析方法可以为通过靶分子与脂膜的温度诱导动力学来估计它们之间的相互作用提供一个新的视角。根据这些结果，我们的方法可用于分析脂质膜-寡核苷酸相互作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Interaction Analysis between Cationic Lipid and Oligonucleotide with a Lipid Membrane-Immobilized Monolith Silica Column: A High-Performance Liquid Chromatography Approach

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Interaction Analysis between Cationic Lipid and Oligonucleotide with a Lipid Membrane-Immobilized Monolith Silica Column: A High-Performance Liquid Chromatography Approach

Understanding the interactions between lipid membranes and nucleotide drugs is crucial for nucleic acid therapy. Although several methods have been employed to evaluate nucleotide–lipid membrane interactions, these interactions can be complex; this complexity arises from how external factors, such as ionic strength or temperature, influence the lipid membrane’s overall properties. In this study, we prepared a lipid membrane-immobilized monolithic silica (LMiMS) column for high-performance liquid chromatography (HPLC) analysis to understand interactions between the lipid membrane and nucleic acid. First, the Raman shift, zeta potential, fluidity, and polarity of the LMiMS-column membrane were analyzed and compared to dispersed liposomes (not immobilized) with the same lipid composition. The results indicated that the column can effectively imitate the temperature-dependent properties of the lipid membrane, suggesting that the immobilized lipid membrane can be used as a model of dispersed liposomal membranes. Subsequently, HPLC was performed to analyze the interaction between the lipid membrane and oligonucleotides. The retention factor k was determined as an interaction factor between the LMiMS column and nucleic acid models (poly 10, 25, and 50mer dC) at various temperatures and mobile phase salt concentrations. The results revealed that changes in membrane interaction were significant by the phase state and salt concentration. Further analysis of the retention factor k showed that the interaction is weak below the phase transition temperature but strong above the phase transition temperature. The results indicate that membrane properties (rigidity and polarity) are also related to membrane interaction, which can be evaluated with the LMiMS column. This analytical method can provide a new perspective on estimating the interactions between target molecules and the lipid membrane through their temperature-induced dynamics. From these results, our method could be useful for analyzing lipid membrane–oligonucleotide interactions.

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来源期刊

Langmuir 化学-材料科学：综合

CiteScore

6.50

自引率

10.30%

发文量

1464

审稿时长

2.1 months

期刊介绍： Langmuir is an interdisciplinary journal publishing articles in the following subject categories: Colloids: surfactants and self-assembly, dispersions, emulsions, foams Interfaces: adsorption, reactions, films, forces Biological Interfaces: biocolloids, biomolecular and biomimetic materials Materials: nano- and mesostructured materials, polymers, gels, liquid crystals Electrochemistry: interfacial charge transfer, charge transport, electrocatalysis, electrokinetic phenomena, bioelectrochemistry Devices and Applications: sensors, fluidics, patterning, catalysis, photonic crystals However, when high-impact, original work is submitted that does not fit within the above categories, decisions to accept or decline such papers will be based on one criteria: What Would Irving Do? Langmuir ranks #2 in citations out of 136 journals in the category of Physical Chemistry with 113,157 total citations. The journal received an Impact Factor of 4.384*. This journal is also indexed in the categories of Materials Science (ranked #1) and Multidisciplinary Chemistry (ranked #5).