Ligand coated nanosphere adhesion to E- and P-selectin under static and flow conditions.

Autor: Blackwell JE; The Department of Biomedical Engineering, The University of Memphis, TN, USA., Dagia NM, Dickerson JB, Berg EL, Goetz DJ
Jazyk: angličtina
Zdroj: Annals of biomedical engineering [Ann Biomed Eng] 2001 Jun; Vol. 29 (6), pp. 523-33.
DOI: 10.1114/1.1376697
Abstrakt: 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.
Databáze: MEDLINE