Blackwell J E, Dagia N M, Dickerson J B, Berg E L, Goetz D J
The Department of Biomedical Engineering, The University of Memphis, TN, USA.
Ann Biomed Eng. 2001 Jun;29(6):523-33. doi: 10.1114/1.1376697.
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.
血管内皮细胞粘附分子（ECAMs）在血管内皮腔表面的异质性分布为将药物输送到特定组织提供了机会。通过使用外表面带有选择性表达的ECAM配体的载体可以实现靶向。载体将在流体动力学环境中与内皮相互作用，并且在许多此类方案中会使用纳米颗粒。目前尚不清楚各种参数（例如，配体-ECAM化学性质、流体剪切力）对纳米颗粒与内皮的粘附会有什么作用。为了促进该领域的研究，我们开发了一种原型体外模型，用于研究纳米颗粒的粘附。我们用识别ECAMs E-选择素和P-选择素的人源化单克隆抗体（HuEP5C7.g2）包被聚苯乙烯纳米球。粘附试验表明，HuEP5C7.g2纳米球对表达选择素的细胞单层表现出增强的特异性粘附，并且这种粘附会受到流体剪切力的影响。这些结果：（i）强烈表明HuEP5C7.g2可用于将纳米颗粒靶向到表达选择素的内皮；（ii）证明流体剪切力会影响纳米颗粒的粘附；（iii）定义了一个可用于研究各种系统参数对纳米颗粒粘附影响的系统。
