Compositions and Methods for Producing Vascular Occlusion Using a Solid-Phase Platelet Binding Agent

Abstract

The present invention relates generally to methods and compositions for targeting and delivering solid-phase platelet-dependent vascular occlusion agents. In particular, particles or coils or stents coated with platelet binding agents are directed to target vasculature, such as the vasculature of solid tumor masses or AV-malformations or aneurysms or endoleaks; the solid-phase agent then binds and activates platelets, which in turn bind and activate other platelets. This process results in the rapid formation of a platelet-mediated thrombus about the solid-phase agent causing vessel occlusion.

1 . A composition for inducing thrombus formation in vivo comprising a solid-phase agent comprising a platelet-specific component; wherein upon delivery to target vasculature the platelet-binding component binds platelets onto the solid-phase agent, induces platelet activation and allows a thrombus to form. 
     
     
         2 . The composition of  claim 1  where the solid-phase agent is a particle. 
     
     
         3 . The composition of  claim 2  where the particle is a microsphere. 
     
     
         4 . The composition of  claim 2  where the particle is macro-aggregated albumin. 
     
     
         5 . The composition of  claim 4  where the particles range in size from about 5 to about 500 microns. 
     
     
         6 . The composition of  claim 4  where the particles range in size from about 30 to about 150 microns. 
     
     
         7 . The composition of  claim 1  where the solid-phase agent is a coil. 
     
     
         8 . The composition of  claim 1  where the solid-phase agent is a stent. 
     
     
         9 . The composition of  claim 1  wherein the platelet-specific component comprises at least one of the components selected from the group consisting of von Willebrand factor, osteopontin, fibrinogen, fibrin, fibronectin, vitronectin, collagen, thrombospondin, laminin, heparin, heparan sulfate, chondroitin sulfate, phospholipase A2, matrix metalloproteinases, thrombin, glass, sialyl-lewis X, fibulin-1, PECAM, ICAM-1, ICAM-2, p-selectin ligand, MAC-1, LFA-1, portions of any of the above, and functional equivalents of any of the above, natural or synthetic. 
     
     
         10 . The composition of  claim 1  wherein the platelet-specific component is recombinant VWF. 
     
     
         11 . The composition of  claim 1  wherein the platelet-specific component is mammalian VWF. 
     
     
         12 . The composition of  claim 1  wherein the platelet-specific component is of human origin. 
     
     
         13 . The composition of  claim 1  wherein the platelet-specific component is of porcine origin. 
     
     
         14 . The composition of  claim 1  wherein the solid-phase agent contains a targeting moiety. 
     
     
         15 . The composition of  claim 1  wherein the targeting moiety is directed to at least one antigen on the target vasculature. 
     
     
         16 . The composition of  claim 1  wherein the solid-phase agent further comprises a ligand for binding platelets to the solid phase agent. 
     
     
         17 . The composition of  claim 1  wherein the solid-phase agent is radiolabeled with sodium pertechnetate Tc 99m. 
     
     
         18 . A composition for inducing thrombus formation comprising a solid-phase platelet-binding agent having a first binding component and a second binding component, said first binding component comprising a binding region for binding the solid-phase agent to a ligand/receptor complex but not the ligand or receptor alone; said second binding component comprising a binding region for platelets. 
     
     
         19 . A composition for inducing thrombus formation comprising a solid-phase agent having a first binding component and a second binding component, said first binding component comprising a binding region for binding the binding component to an epitope on a pre-determined site; said second binding component comprising a binding region for platelets. 
     
     
         20 . The composition of  claim 1  wherein the solid phase agent is 10 microns to 7000 microns.