Presence of hydrodynamic forces and blood cell interactions. To date, it is not clear what effect the nanoscale coating of plasma proteins onto VTC surfaces may have on their BMN673 PARP inhibitor interaction with the vascular wall in the complex environment of human blood flow, which is critical for any intravenously administered VTC system designed for human use. In general, the capture and binding of targeted particles to a reactive surface from flow can occur on the order of one to tens of seconds depending on the kinetics of ligand/receptor interaction and provided there is no steric hindrance to receptor-ligand contact or physical barrier to particle localization to the surface. In several experimental works with simple buffer or human blood flows in vitro, polystyrene or silica-based microparticles have been shown to effectively localize and bind to the vascular wall. However, limited work currently exist in the literature on the flow adhesion to reactive surfaces of poly based-particles that are ubiquitously proposed for use as VTCs, all of which have reported on adhesion only in buffer flow assays. Here, we investigate the role of the plasma protein corona in the adhesion of poly particles to a vascular wall model from human blood flow via in vitro assays. Specifically, we characterized the adhesion of sLea-conjugated PLGA particles in laminar and pulsatile human blood flows to a monolayer of activated endothelial cells in a parallel plate flow chamber. sLea is a carbohydrate ligand with favorable binding kinetics to E-selectin, overexpressed by inflamed ECs, in flow. This ligand has also previously been proposed for targeting therapeutics in many diseases. The data presented here show that vascular-targeted PLGA particles do not effectively adhere to inflamed ECs in human blood flow of different magnitude and flow pattern, an effect that was not observed for PS spheres. We conclude that this phenomena is linked to the unique adsorption of specific “negative proteins” onto the surface of PLGA particles. This conclusion is supported by data from control experiments that shows higher binding of PLGA particles with buffer and RBC-in-buffer flows compare to the values observed in whole blood or plasma only flows of the same flow type and shear magnitude. Also, a preliminary mass spectrometry analysis of the hard protein corona on particles revealed unique proteins, mostly immunoglobulin subclasses/ subtypes, found in the protein corona on PLGA but not in the corona on PS particles when exposed to the same donor blood. It is likely that PS do not exhibit reduced adhesion in human blood flow due to the critical negative plasma proteins having a low affinity for these materials. This assertion that different material chemistry affects the type of adsorbed plasma proteins on particles of similar size and surface charge is in line with a previous report by others.