Mulder Willem J M, Strijkers Gustav J, Griffioen Arjan W, van Bloois Louis, Molema Grietje, Storm Gert, Koning Gerben A, Nicolay Klaas
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB, The Netherlands.
Bioconjug Chem. 2004 Jul-Aug;15(4):799-806. doi: 10.1021/bc049949r.
Pegylated paramagnetic and fluorescent immunoliposomes were designed to enable the parallel detection of the induced expression of molecular markers on endothelial cells with magnetic resonance imaging (MRI) and fluorescence microscopy. MRI is capable of three-dimensional noninvasive imaging of opaque tissues at near cellular resolution, while fluorescence microscopy can be used to investigate processes at the subcellular level. As a model for the expression of a molecular marker, human umbilical vein endothelial cells (HUVEC) were treated with the pro-inflammatory cytokine tumor necrosis factor alpha (TNFalpha) to upregulate the expression of the adhesion molecule E-selectin/CD62E. E-selectin-expressing HUVEC were incubated with pegylated paramagnetic fluorescently labeled liposomes carrying anti-E-selectin monoclonal antibody as a targeting ligand. Both MRI and fluorescence microscopy revealed the specific association of the liposomal MR contrast agent with stimulated HUVEC. This study suggests that this newly developed system may serve as a useful diagnostic tool to investigate pathological processes in vivo with MRI.
聚乙二醇化顺磁性荧光免疫脂质体的设计目的是能够通过磁共振成像(MRI)和荧光显微镜并行检测内皮细胞上分子标记物的诱导表达。MRI能够以接近细胞分辨率对不透明组织进行三维无创成像,而荧光显微镜可用于研究亚细胞水平的过程。作为分子标记物表达的模型,用人促炎细胞因子肿瘤坏死因子α(TNFα)处理人脐静脉内皮细胞(HUVEC),以上调粘附分子E-选择素/CD62E的表达。将表达E-选择素的HUVEC与携带抗E-选择素单克隆抗体作为靶向配体的聚乙二醇化顺磁性荧光标记脂质体一起孵育。MRI和荧光显微镜均显示脂质体MR造影剂与受刺激的HUVEC有特异性结合。该研究表明,这种新开发的系统可能作为一种有用的诊断工具,用于在体内通过MRI研究病理过程。