Glycoprotein Ib Functionalized-Nanoparticles for Targeted Drug Delivery Under High Shear Conditions

Atherothrombosis is a leading cause of acute coronary syndrome. At atherothrombotic stenosis sites, platelets may undergo a mechanical based activation due to elevated shear stress that exists at these sites. Under high shear stress, von Willebrand factor (VWF), a glycoprotein found in plasma, interacts with glycoprotein Ib (GPIb), a platelet receptor and mediates platelets’ adhesion and aggregation. In our research, we aim to design and fabricate GPIb-functionalized nanoparticles as potential targeted nano-therapeutics to atherothrombotic sites.

We study experimentally using in vitro microfluidic models the adhesion kinetics, under flow, of glycocalicyn (the extra-cellular fraction of GPIb) functionalized nanoparticles to a collagen-coated surface or to fixed VWF-platelet complexes. Using time-lapse confocal microscopy the adhesion kinetics of fluorescently tagged particles can be monitored under flow. Our preliminary results show specific adhesion of these particles to VWF-coated surfaces in comparison to collagen-coated surfaces under high shear stress.