The Endothelial Glycocalyx Controls Interactions of Quantum Dots with the Endothelium and Their Translocation across the Blood-Tissue Border
The Endothelial Glycocalyx Controls Interactions of Quantum Dots with the Endothelium and Their Translocation across the Blood-Tissue Border
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DOI：
10.1021/acsnano.6b06812
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发表时间：
2017-02-01
期刊：
影响因子：
17.1
通讯作者：
Krombach, Fritz
中科院分区：
文献类型：
--
作者：
Uhl, Bernd;Hirn, Stephanie;Krombach, Fritz
纳米颗粒 (NP) 是一种外部尺寸小于 100 nm 的颗粒，其工程技术的进步导致纳米材料在生物医学领域的利用不断增加。然而，它们用于诊断和治疗应用的先决条件是有针对性地递送到损伤部位。血源性纳米颗粒与血管内皮之间的相互作用是将纳米颗粒输送到患病组织的关键步骤。在这里，我们表明，内皮糖萼构成了覆盖血管腔表面的糖蛋白多糖网络，可以有效控制羧基功能化量子点与微血管内皮的相互作用。研究发现内皮糖萼的糖胺聚糖物理覆盖内皮粘附和信号分子，从而防止内皮附着、摄取和这些纳米颗粒穿过血管壁的不同层的易位。相反，在缺血再灌注的病理条件下，内皮糖萼的降解促进了这些纳米颗粒与微血管内皮细胞的相互作用，从而将受损的内皮糖萼确定为血液组织边界的重要元素，促进纳米材料靶向递送至患病组织。
Advances in the engineering of nanoparticles (NPs), which represent particles of less than 100 nm in one external dimension, led to an increasing utilization of nanomaterials for biomedical purposes. A prerequisite for their use in diagnostic and therapeutic applications, however, is the targeted delivery to the site of injury. Interactions between blood-borne NPs and the vascular endothelium represent a critical step for nanoparticle delivery into diseased tissue. Here, we show that the endothelial glycocalyx, which constitutes a glycoprotein polysaccharide meshwork coating the luminal surface of vessels, effectively controls interactions of carboxyl-functionalized quantum dots with the micro vascular endothelium. Glycosaminoglycans of the endothelial glycocalyx were found to physically cover endothelial adhesion and signaling molecules, thereby preventing endothelial attachment, uptake, and translocation of these nanoparticles through different layers of the vessel wall. Conversely, degradation of the endothelial glycocalyx promoted interactions of these nanoparticles with microvascular endothelial cells under the pathologic condition of ischemia-reperfusion, thus identifying the injured endothelial glycocalyx as an essential element of the blood-tissue border facilitating the targeted delivery of nanomaterials to diseased tissue.