(512b) Influence of Size and Shape of Vascular-Targeting Carriers On Neutrophil Adhesion to An Inflamed Endothelial Monolayer in Blood Flow

Ligand-based targeting of diseased vasculature is attractive for improving diagnostics and therapeutic treatment of cardiovascular diseases.  Many cardiovascular events, including plaque development and reperfusion-injury, originate at sites of vascular inflammation.  Receptors such as E-selectin are often targeted for imaging and drug delivery because of its specific upregulation by endothelial cells, the monolayer of cells lining the internal wall of blood vessels, during inflammation.  Researchers have investigated the effects of size and shape on the adhesion of E-selectin targeting carriers to inflamed endothelial cells; however, little work has been done in the presence of blood cells - specifically neutrophils, which interact with the vessel wall through E-selectin during an inflammatory response. Little is known about particle-neutrophil dynamics in blood flow and whether targeted carriers affect neutrophil adhesion to the inflamed vessel wall.  Here we investigate the effect of carrier size and shape on neutrophil adhesion to an inflamed endothelial monolayer using E-selectin targeting polystyrene microspheres (0.5, 2 and 5 µm) and ellipsoidal rods in human blood flow at physiological shear conditions using a parallel plate flow chamber.  Our results show that E-selectin targeting carriers influence neutrophil adhesion and the response is dependent on the carrier’s size, shape, and hemodynamics.