Center for Applied Research in Applied Biomedical Mass Spectrometry (ABIMAS). Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.
Instrumental Analytics and Bioanalytics, Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.
Sci Rep. 2016 Sep 21;6:33791. doi: 10.1038/srep33791.
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.
磷脂具有极好的生物相容性，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。本研究提出基质辅助激光解吸/电离质谱成像（MALDI MSI）作为替代方法，用于对小鼠组织中的脂质体药物载体进行无标记的分子体外成像。为此，将吲哚菁绿作为货物和两种脂质体标记物（1,2-二棕榈酰基-sn-甘油-3-磷酸甘油（DPPG）和与单分散聚乙二醇（PEG36-DSPE）偶联的 1,2-二硬脂酰基-sn-甘油-3-磷酸乙醇胺）掺入脂质体载体中，并施用于小鼠。我们使用两种脂质标记物的 MALDI MSI 在正离子和负离子模式下进行可视化，以观察脂质体的完整性和在小鼠器官中的分布。对同一组织切片中的血红蛋白进行额外的 MALDI MSI，并对脂质标记物和血红蛋白的共现进行逐像素计算分析，作为脂质体定位于实质或血管中的指标。我们的概念验证研究表明，脂质体成分和吲哚菁绿分布到所有研究的器官中。
