Ligand coated nanosphere adhesion to E- and P-selectin under static and flow conditions
Ligand coated nanosphere adhesion to E- and P-selectin under static and flow conditions
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DOI：
10.1114/1.1376697
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发表时间：
2001-06-01
影响因子：
3.8
通讯作者：
Goetz, DJ
中科院分区：
文献类型：
--
作者：
Blackwell, JE;Dagia, NM;Goetz, DJ
内皮细胞粘附分子（ECAM）在血管内皮细胞表面的不均匀分布为药物递送到选择性组织提供了机会。靶向可以通过使用其外表面具有用于选择性表达的ECAM的配体的载体来实现。载体将在流体动力学环境中与内皮相互作用，并且在许多这些方案中将使用纳米颗粒。目前还不清楚各种参数（例如，配体-ECAM化学、流体剪切）将对纳米颗粒与内皮的粘附产生影响。为了促进这一领域的研究，我们已经开发了一个原型的体外模型，可以调查纳米颗粒的粘附。我们用识别ECAM E-和P-选择素的人源化mAb（HuEP 5C7.g2）包被聚苯乙烯纳米球。粘附测定揭示HuEP 5C7.g2纳米球表现出对选择素呈递细胞单层的增强的特异性粘附，并且粘附可受流体剪切的影响。这些结果;（i）强烈表明HuEP 5C7.g2可用于将纳米颗粒靶向选择素呈递内皮;（ii）证明流体剪切可影响纳米颗粒粘附;和（iii）定义可用于研究各种系统参数对纳米颗粒粘附的影响的系统。(C)2001生物医学工程学会。
The heterogeneous distribution of endothelial cell adhesion molecules (ECAMs) on the lumenal surface of vascular endothelium provides an opportunity to deliver drugs to select tissues. The targeting could be achieved by using carriers whose outer surface has a Ligand for a selectively expressed ECAM. The carriers would interact with the endothelium in a fluid dynamic environment and in many of these schemes nanoparticles would be used. It is unclear what role various parameters (e.g., ligand-ECAM chemistry, fluid shear) will have on the adhesion of the nanoparticles to the endothelium. To facilitate studies in this area, we have developed a prototypical in vitro model that allows investigation of nanoparticle adhesion. We coated polystyrene nanospheres with a humanized mAb (HuEP5C7.g2) that recognizes the ECAMs E- and P-selectin. Adhesion assays revealed that HuEP5C7.g2 nanospheres exhibit augmented, specific adhesion to selectin presenting cellular monolayers and that the adhesion can be affected by the fluid shear. These results; (i) strongly suggest that HuEP5C7.g2 could be used to target nanoparticles to selectin presenting endothelium; (ii) demonstrate that fluid shear can affect nanoparticle adhesion; and (iii) define a system which can be used to study the effects of various system parameters on nanoparticle adhesion. (C) 2001 Biomedical Engineering Society.