The final goal of our research is to develop smart particles to stop internal hemorrhage at local sites. To accomplish this goal, we are combining multiple approaches in four collaborating laboratories to define threshold levels of activators of blood clotting such that the candidate clotting activators will circulate in the blood at below the threshold necessary to trigger clotting, but accumulation of the activators at sites of internal injury/bleeding will cause the local concentration of clotting activators to exceed the clotting threshold and restore hemostasis. The approaches being used include the development of novel chemistries for attaching inorganic polyphosphate (polyP; a potent trigger and accelerator of blood clotting) to nanoscale solid supports, development of candidate nanoparticles with varying abilities to trigger and/or accelerate blood clotting, and defining the threshold levels under which these particles will or will not trigger blood clotting.
