Our primary research focus is the therapeutic targeting of platelets in thrombotic disease. This work involves the synthesis of gold-coated magnetite nanoparticles; their conjugation with fibrinogen, a protein that will carry them specifically to activated platelets (as opposed to unactivated platelets); and their binding to the activated platelet surface. Nanoparticle-labeled platelets are then exposed to an oscillating magnetic field such as can be found in an MRI, where inductive heating dependent on the presence of magnetic iron oxide produces exquisitely localized platelet membrane damage and subsequent destruction of labeled cells. This novel approach to platelet targeting has applications for treating arterial thrombosis, and has especially high potential in the treatment of thrombotic stroke, for which approximately 95% of all patients receive only supportive, not interventional, care. Even if only a small percentage of those stroke patients would ultimately benefit from this treatment approach, the impact upon our health care system would be tremendous. Our preliminary in vitro data all suggest that our method will be successful, even in an established thrombus in the presence of plasma concentration of fibrinogen. This leaves our lab ready to move on to in vivo experiments in a mouse model of carotid artery thrombosis. We have also begun testing our targeting and inductive heating method in other model systems, such as tumor cells, where a surface marker that distinguishes target cells from normal cells can be exploited.
Our expertise in nanoparticle synthesis can be applied to other systems. For example, we are testing whether platelet- or plasma-derived factor V is preferentially incorporated into coagulation complexes on the surface of activated platelets. We identify the proteins using colloidal nanoparticles of different sizes and shapes synthesized by chemical reduction of salts of different electron dense metals. We also use this method to study the expression and distribution of tissue factor, the physiologically relevant initiator of blood coagulation, on freshly isolated blood cells and on cultured cell lines.