Molecular imaging of brain localization of liposomes in mice using MALDI mass spectrometry.

Molecular imaging of brain localization of liposomes in mice using MALDI mass spectrometry.
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DOI:
10.1038/srep33791
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发表时间:
2016-09-21
期刊:
影响因子:
4.6
通讯作者:
Hopf C
Hopf C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fülöp A;Sammour DA;Erich K;von Gerichten J;van Hoogevest P;Sandhoff R;Hopf C

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磷脂具有良好的生物相容性,因此常被用作脂质体药物载体的主要成分。在传统的生物分析中,使用放射性标记的脂质体成分来评估脂质体药物载体的体内分布。本研究提出了基质辅助激光解吸/电离质谱成像(MALDI MSI)作为一种替代的、无标记的方法,用于小鼠组织中脂质体药物载体的离体分子成像。为此,将吲哚菁绿作为载体和两种脂质体标记物,1,2-双棕榈酰- n-甘油-3-磷酸甘油(DPPG)和1,2-二硬脂酰- n-甘油-3-磷酸乙醇胺偶联单分散聚乙二醇(PEG36-DSPE)掺入脂质体载体中,并给药给鼠。我们在正负离子模式下使用MALDI MSI对两种脂质标记物进行了脂质体完整性和分布在小鼠器官中的可视化。同一组织切片中血红蛋白的额外MSI以及脂质标记物与血红蛋白共存的逐像素计算分析可作为脂质体定位于实质或血管的指标。我们的概念验证研究表明,脂质体成分和吲哚菁绿分布在所有研究器官中。
Phospholipids have excellent biocompatibility and are therefore often used as main components of liposomal drug carriers. In traditional bioanalytics, the in-vivo distribution of liposomal drug carriers is assessed using radiolabeled liposomal constituents. This study presents matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) as an alternative, label-free method for ex-vivo molecular imaging of liposomal drug carriers in mouse tissue. To this end, indocyanine green as cargo and two liposomal markers, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated with monodisperse polyethylene glycol (PEG36-DSPE) were incorporated into liposomal carriers and administered to mice. We used MALDI MSI of the two lipid markers in both positive and negative ion mode for visualization of liposome integrity and distribution in mouse organs. Additional MSI of hemoglobin in the same tissue slice and pixel-by-pixel computational analysis of co-occurrence of lipid markers and hemoglobin served as indicator of liposome localization either in parenchyma or in blood vessels. Our proof-of-concept study suggests that liposomal components and indocyanine green distributed into all investigated organs.
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影响因子: 7.4
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