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小角中子散射揭示了嵌入OprF孔蛋白的脂质体的纳米结构。

Small-Angle Neutron Scattering Reveals the Nanostructure of Liposomes with Embedded OprF Porins of .

作者信息

Spinozzi Francesco, Alcaraz Jean-Pierre, Ortore Maria Grazia, Gayet Landry, Radulescu Aurel, Martin Donald K, Maccarini Marco

机构信息

Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy.

Univ. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France.

出版信息

Langmuir. 2022 Dec 13;38(49):15026-15037. doi: 10.1021/acs.langmuir.2c01342. Epub 2022 Dec 2.

DOI:10.1021/acs.langmuir.2c01342
PMID:36459683
Abstract

The use of liposomes as drug delivery systems emerged in the last decades in view of their capacity and versatility to deliver a variety of therapeutic agents. By means of small-angle neutron scattering (SANS), we performed a detailed characterization of liposomes containing outer membrane protein F (OprF), the main porin of the bacterium outer membrane. These OprF-liposomes are the basis of a novel vaccine against this antibiotic-resistant bacterium, which is one of the main hospital-acquired pathogens and causes each year a significant number of deaths. SANS data were analyzed by a specific model we created to quantify the crucial information about the structure of the liposome containing OprF, including the lipid bilayer structure, the amount of protein in the lipid bilayer, the average protein localization, and the effect of the protein incorporation on the lipid bilayer. Quantification of such structural information is important to enhance the design of liposomal delivery systems for therapeutic applications.

摘要

鉴于脂质体能够递送多种治疗剂且具有多功能性,在过去几十年中,脂质体作为药物递送系统开始出现。通过小角中子散射(SANS),我们对含有外膜蛋白F(OprF)的脂质体进行了详细表征,OprF是细菌外膜的主要孔蛋白。这些OprF脂质体是一种针对这种耐抗生素细菌的新型疫苗的基础,该细菌是主要的医院获得性病原体之一,每年导致大量死亡。我们通过创建的特定模型分析SANS数据,以量化有关含有OprF的脂质体结构的关键信息,包括脂质双层结构、脂质双层中的蛋白量、蛋白的平均定位以及蛋白掺入对脂质双层的影响。量化此类结构信息对于改进用于治疗应用的脂质体递送系统的设计非常重要。

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