链长依赖性阿霉素嵌入聚乙二醇化脂质体引起的脂膜结构变化。

IF 6.1 3区 材料科学 Q1 Biochemistry, Genetics and Molecular Biology
Journal of Applied Crystallography Pub Date : 2025-05-29 eCollection Date: 2025-06-01 DOI:10.1107/S1600576725003577
Jia-Jhen Kang, Zhih-Chen Huang, Li-Wen Tang, Chun-Jen Su, Hua-De Gao, Hsien-Ming Lee, U-Ser Jeng
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引用次数: 0

摘要

由于在运送疫苗、营养物质和药物分子(如阿霉素(DOX))方面的实际应用,聚乙二醇(乙二醇)接枝(聚乙二醇化)脂质体越来越受到关注。聚乙二醇化脂质体作为封闭在单层囊泡内的棒状晶体,具有携带DOX的能力。本研究通过同时使用小角和广角x射线散射(SWAXS),并辅以集成的不对称流场-流分析系统,结合多角度光散射、动态光散射和折射率检测,解决了以前未解决的DOX是否插入脂质体双层的问题。所使用的dox负载聚乙二醇脂质体由磷脂酰胆碱(N:0 PC)脂质组成,脂质链长度N = 18、20和22,脂质:胆固醇:DSPE-PEG2000的固定摩尔比为45:50:5。SWAXS分析显示,棒状DOX纳米晶体(长度约为70-95 nm,直径约为14 nm)被包裹在聚乙二醇化脂质体中,所有三种脂质类型都表现出不同的膜结构响应。值得注意的是,22:0 PC脂质体表现出明显的dox诱导的脂链包装破坏,并伴有外小叶中磷酸基团的增强排列。与此一致的是,低温电子显微镜成像显示在dox负载的22:0 PC脂质体中明显的多面膜形态。这种表面现象是由于延长的脂肪链超过胆固醇饱和极限所产生的过量疏水核心区域内DOX的积累。这些富含dox的结构域局部使膜变硬,促进刚性面结构的形成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Changes of the lipid membrane structures caused by chain-length-dependent doxorubicin embedment in PEGylated liposomes.

Poly(ethyl-ene glycol)-grafted (PEGylated) liposomes receive increasingly more attention due to their practical applications in delivering vaccines, nutrients and drug molecules such as doxorubicin (DOX). PEGylated liposomes have been well documented for their capability in carrying DOX as rod-like crystallites enclosed inside the unilamellar vesicles. This study addresses the previously unresolved question of whether DOX intercalates into liposome bilayers by employing simultaneous small- and wide-angle X-ray scattering (SWAXS), complemented by an integrated asymmetric flow field-flow fractionation system coupled with multi-angle light scattering, dynamic light scattering and refractive index detection. The DOX-loaded PEGylated liposomes used are composed of phosphatidylcholine (N:0 PC) lipids, with different lipid chain lengths N = 18, 20 and 22, and a fixed molar ratio of lipid:cholesterol:DSPE-PEG2000 of 45:50:5. SWAXS analysis reveals that rod-like DOX nanocrystallites-approximately 70-95 nm in length and 14 nm in diameter-are encapsulated within the PEGylated liposomes across all three lipid types, with each exhibiting distinct membrane structural responses to DOX incorporation. Notably, 22:0 PC liposomes demonstrate significant DOX-induced disruption of lipid chain packing, accompanied by enhanced alignment of phosphate headgroups in the outer leaflet. Consistently, cryo-EM imaging reveals pronounced faceted membrane morphologies in DOX-loaded 22:0 PC liposomes. This faceting phenomenon is attributed to the accumulation of DOX within the excess hydro-phobic core regions created by the extended aliphatic chains beyond the cholesterol saturation limit. These DOX-enriched domains locally stiffen the membrane, promoting the formation of rigid, faceted structures.

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来源期刊
CiteScore
10.00
自引率
3.30%
发文量
178
审稿时长
4.7 months
期刊介绍: Many research topics in condensed matter research, materials science and the life sciences make use of crystallographic methods to study crystalline and non-crystalline matter with neutrons, X-rays and electrons. Articles published in the Journal of Applied Crystallography focus on these methods and their use in identifying structural and diffusion-controlled phase transformations, structure-property relationships, structural changes of defects, interfaces and surfaces, etc. Developments of instrumentation and crystallographic apparatus, theory and interpretation, numerical analysis and other related subjects are also covered. The journal is the primary place where crystallographic computer program information is published.
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