Platelets as Contractile Nanomachines for Targeting Drug Delivery in Hemostasis and Thrombosis

Abstract : For this grant, we proposed to apply different nanocarrier synthesis techniques, modulate fibrinogen density and structure on the nanocarrier surface (which both affect platelet adhesion), the nanocarrier stiffness (which affects the force of platelet contraction and platelet adhesion), and the size of the nanocarrier. In addition, using a novel endothelial-ized microfluidic system, we proposed to investigate how external factors such as flow and thrombin concentration affect drug release. The proposed proof-of-concept experiments will validate our concept of platelet contraction-controlled nanocarriers as a novel and potentially paradigm-shifting strategy for targeted drug delivery to achieve hemostasis during bleeding. We have since optimized our nanocarrier synthesis protocol and as well as fibrinogen density and structure on the nanocarrier surface. Finally we determined that physiologic arterial flow conditions optimize the release of our nanocarriers work and have also determined that nanocarrier release is dependent on local thrombin concentration.