Institute of Diagnostic and Interventional Radiology, Experimental Radiology, Jena University Hospital, Am klinikum 1, 07747 Jena, Germany.
Department of Pharmaceutical Technology, Friedrich-Schiller-University Jena, Lessingstrasse 8, 07743 Jena, Germany.
Biochim Biophys Acta Gen Subj. 2018 Jun;1862(6):1389-1400. doi: 10.1016/j.bbagen.2018.03.012. Epub 2018 Mar 13.
Endoglin (CD105) is overexpressed on tumor cells and tumor vasculatures, making it a potential target for diagnostic imaging and therapy of different neoplasms. Therefore, studies on nanocarrier systems designed for endoglin-directed diagnostic and drug delivery purposes would expose the feasibility of targeting endoglin with therapeutics.
Liposomes carrying high concentrations of a near-infrared fluorescent dye in the aqueous interior were prepared by the lipid film hydration and extrusion procedure, then conjugated to single chain antibody fragments either selective for murine endoglin (termed mEnd-IL) or directed towards human endoglin (termed hEnd-IL). A combination of Dynamic Light Scattering, electron microscopy, cell binding and uptake assays, confocal microscopy and in vivo fluorescence imaging of mice bearing xenografted human breast cancer and human fibrosarcoma models were implemented to elucidate the potentials of the liposomes.
The mEnd-IL and hEnd-IL were highly selective for the respective murine- and human endoglin expressing cells in vitro and in vivo. Hence, the hEnd-IL bound distinctly to the tumor cells and enabled suitable fluorescence imaging of the tumors, whereas the mEnd-IL bound the tumor vasculature, but also to the liver, kidney and lung vasculature of mice.
The work highlights key differences between targeting vascular (murine) and neoplastic (human) endoglin in animal studies, and suggests that the hEnd-IL can serve as a delivery system that targets human endoglin overexpressed in pathological conditions.
The endoglin-targeting liposomes presented herewith represent strategic tools for the future implementation of endoglin-directed neoplastic and anti-angiogenic therapies.
内皮糖蛋白（CD105）在肿瘤细胞和肿瘤血管中过度表达，使其成为不同肿瘤诊断成像和治疗的潜在靶点。因此，研究针对内皮糖蛋白的诊断和药物递送目的的纳米载体系统将揭示用治疗剂靶向内皮糖蛋白的可行性。
通过脂质膜水化和挤压程序制备在水相内部携带高浓度近红外荧光染料的脂质体，然后将其与单链抗体片段缀合，这些片段选择性地针对鼠内皮糖蛋白（称为 mEnd-IL）或针对人内皮糖蛋白（称为 hEnd-IL）。实施动态光散射、电子显微镜、细胞结合和摄取测定、共聚焦显微镜以及携带异种移植人乳腺癌和人纤维肉瘤模型的小鼠的体内荧光成像，以阐明脂质体的潜力。
mEnd-IL 和 hEnd-IL 在体外和体内对各自表达鼠和人内皮糖蛋白的细胞具有高度选择性。因此，hEnd-IL 与肿瘤细胞特异性结合，并能够对肿瘤进行适当的荧光成像，而 mEnd-IL 与肿瘤血管结合，但也与小鼠的肝、肾和肺血管结合。
这项工作强调了在动物研究中靶向血管（鼠）和肿瘤（人）内皮糖蛋白之间的关键差异，并表明 hEnd-IL 可作为一种递送系统，靶向病理条件下过度表达的人内皮糖蛋白。
本文提出的内皮糖蛋白靶向脂质体代表了未来实施内皮糖蛋白靶向肿瘤和抗血管生成治疗的战略工具。
