Adhesion of bio-functionalized ultrasound microbubbles to endothelial cells by targeting to vascular cell adhesion molecule-1 under shear flow.
Adhesion of bio-functionalized ultrasound microbubbles to endothelial cells by targeting to vascular cell adhesion molecule-1 under shear flow.
复制标题
剪切流下生物功能化超声微泡靶向血管细胞粘附分子1对内皮细胞的粘附
DOI：
10.2147/ijn.s24808
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发表时间：
2011
影响因子：
8
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Yang H;Xiong X;Zhang L;Wu C;Liu Y
在内皮功能障碍或炎症激活过程中，某些内皮细胞黏附分子的表达增加。这导致了利用微泡进行靶向分子成像或药物输送的概念。在这种方法中，构建了与特定疾病部位表达的受体具有特定配体的微泡。本研究旨在设计一种新型的生物功能化微泡(血管细胞黏附分子1[VCAM-1]靶向微泡)，并确定VCAM-1靶向微泡是否具有对内毒素(LPS)激活的内皮细胞的特异性黏附作用。我们的数据显示，VCAM-1在脂多糖激活的体外内皮细胞和体内大鼠动脉粥样硬化模型中的内皮细胞中的表达显著上调。通过生物素-亲和素桥联化学方法将抗VCAM-1的单抗偶联到微泡的外壳上，从而设计出靶向微泡。在两种剪应力条件(6.3和10.4dynes/cm2)下，在流动室中评估微泡与内皮细胞的黏附。我们的数据表明，微泡的黏附既取决于表面抗VCAM-1抗体的密度，也取决于暴露的剪应力。VCAM-1靶向微泡与脂多糖激活的内皮细胞的粘附力随着表面抗体密度的增加而增加，随着暴露的剪应力的增加而降低。这些发现表明，携带特定配体的微泡在靶向超声、分子成像或超声辅助药物/基因传递应用中具有相当大的潜力。
The expression of certain endothelial cell adhesion molecules is increased during endothelial dysfunction or inflammatory activation. This has led to the concept of using microbubbles for targeted molecular imaging or drug delivery. In this approach, microbubbles with a specific ligand to receptors expressed at the site of specific diseases are constructed. The present study aimed to engineer a novel type of bio-functionalized microbubbles (vascular cell adhesion molecule 1 [VCAM-1]-targeted microbubbles), and determine whether VCAM-1-targeted microbubbles exhibit specific adhesion to lipopolysaccharide (LPS)-activated endothelial cells. Our data showed that VCAM-1 expression was significantly upregulated in both LPS-activated endothelial cells in vitro and endothelium in a rat atherosclerosis model in vivo. Targeted microbubbles were designed by conjugating anti-VCAM-1 monoclonal antibodies to the shell of microbubbles using biotin–avidin bridging chemistry methods. Microbubble adhesion to endothelial cells was assessed in a flow chamber at two shear stress conditions ( 6.3 and 10.4 dynes/cm2). Our data showed that microbubble adhesion depends on both the surface anti-VCAM-1 antibody densities and the exposed shear stresses. Adhesion of VCAM-1-targeted microbubbles onto LPS-activated endothelial cells increased with the surface antibody densities, and decreased with the exposed shear stresses. These findings showed that the specific ligand-carrying microbubbles have considerable potential in targeted ultrasound molecular imaging or ultrasound-assisted drug/gene delivery applications.