Blood Clot-Targeted Nanoparticles
Emulsions comprising nanoparticles formed from high boiling perfluorochemical substances, said particles coated with a lipid/surfactant coating are made target-specific by directly coupling said nanoparticles to a targeting ligand. The nanoparticle may further include biologically active agents, radionuclides, and/or other imaging agents, and are used to image and/or lyse blood clots in human subjects.
1 . A method to image and/or treat blood clots in human subjects, which method comprises administering to a subject in need of such diagnosis and/or treatment an emulsion of liquid, high-boiling perfluorocarbon-based nanoparticles, wherein said nanoparticles further comprise a coating of lipid/surfactant and which nanoparticles are coupled directly to at least one targeting ligand that is specific for at least one component characterizing blood clots, and
effecting said imaging or treatment.
2 . The method of claim 1 , which comprises administering said composition to said human subject systemically.
3 . The method of claim 2 , wherein said systemic administering is by intravenous administration.
4 . The method of claim 1 , wherein said method comprises administering said composition locally to said clot.
5 . The method of claim 1 , which method comprises obtaining an image of said clot using ultrasound, MRI or a radionuclide.
6 . The method of claim 1 , which method comprises effecting lysis or constrained propagation of said clot.
7 . The method of claim 1 , wherein said targeting ligand is coupled covalently to a component of the lipid/surfactant coating.
8 . The method of claim 1 , wherein said ligand binds specifically to fibrin.
9 . The method of claim 1 , wherein said nanoparticles further include at least one magnetic resonance imaging (MRI) contrast agent.
10 . The method of claim 9 , wherein said MRI contrast agent is a chelated paramagnetic ion.
11 . The method of claim 10 , wherein said chelating agent is DOTA and the paramagnetic ion is gadolinium ion.
12 . The method of claim 1 , wherein said nanoparticles further contain at least one radionuclide.
13 . The method of claim 12 , wherein said radionuclide is 99 Tc.
14 . The method of claim 1 , wherein said emulsion further includes at least one biologically active agent.
15 . The method of claim 14 , wherein said biologically active agent is a thrombolytic agent.
16 . The method of claim 1 , wherein said targeting ligand is an antibody, a fragment of an antibody, a peptide, an aptamer, a peptidomimetic or a receptor ligand.
17 . The method of claim 16 , wherein the targeting ligand is an antibody or fragment of an antibody.
18 . The method of claim 17 , wherein said antibody or fragment is humanized.