Blood clot-targeted nanoparticles

• US 20030086867A1
• Filed: 08/20/2002
• Published: 05/08/2003
• Est. Priority Date: 09/24/1999
• Status: Active Grant

• Current Assignee: Barnes-Jewish Hospital (BJC Health System)
• Original Assignee: Barnes-Jewish Hospital (BJC Health System)
• Inventors: Lanza, Gregory, Wickline, Samuel A.
• Granted Patent: US 7,220,401 B2
• Time in Patent Office: Days
• US Class Current: 424/1.11
• CPC Class Codes: A61K 47/6843 the antibody targeting a material from animals or humans
• CPC Class Codes: A61K 47/6907 the form being a microemulsion, nanoemulsion or micelle
• CPC Class Codes: A61K 49/0471 Perflubron, i.e. perfluoroctylbromide, C8F17Br emulsions
• CPC Class Codes: A61K 49/1806 Suspensions, emulsions, colloids, dispersions
• CPC Class Codes: A61K 49/1812 liposomes, polymersomes, e.g. immunoliposomes
• CPC Class Codes: A61K 49/227 Liposomes, lipoprotein vesicles, e.g. LDL or HDL lipoproteins, micelles, e.g. phospholipidic or polymeric
• CPC Class Codes: A61K 51/1227 Micelles, e.g. phospholipidic or polymeric micelles
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

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 nanoparticles may further include biologically active agents, radionuclides, and/or other imaging agents.

Claims

1. A composition comprising 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.

2. The composition of claim 1, wherein said targeting ligand is coupled covalently to a component of the lipid/surfactant coating.

3. The composition of claim 1, wherein said ligand binds specifically to fibrin.

4. The composition of claim 1, wherein said nanoparticles further include at least one magnetic resonance imaging (MRI) contrast agent.

5. The composition of claim 4, wherein said MRI contrast agent is a chelated paramagnetic ion.

6. The composition of claim 5, wherein said chelating agent is diethylenetriaminepentaacetic acid and the paramagnetic ion is gadolinium ion.

7. The composition of claim 1, which further includes at least one biologically active agent.

8. The composition of claim 7, wherein said biologically active agent is a hormone or pharmaceutical.

9. The composition of claim 1, wherein said nanoparticles further contain at least one radionuclide.

10. The composition of claim 9, wherein said radionuclide is ⁹⁹Tc.

11. The composition of claim 1, wherein said targeting ligand is an antibody, a fragment of an antibody, an aptamer, a hormone, peptidomimetic or a receptor ligand.

12. The composition of claim 11, wherein the targeting ligand is an antibody or fragment of an antibody.

13. The composition of claim 12, wherein said antibody or fragment is humanized.

14. A method to obtain a magnetic resonance imaging of a blood clot in a subject, which method comprises administering to said subject the composition of claim 4;

allowing the targeting ligand to couple to the blood clot; and

obtaining an image of said blood clot.

15. A method to deliver a biologically active agent to a blood clot in a subject, which method comprises administering to a subject in need of the presence of such biologically active agent at a blood clot the composition of claim 7;

and

permitting the nanoparticles of said composition to locate in said blood clot,

whereby said biologically active agent is delivered to said blood clot.

16. The method of claim 15, which further includes verifying the location of said nanoparticles by detecting a ¹⁹ F magnetic resonance signal.

17. A method to deliver a radionuclide to a blood clot in a subject, which method comprises administering to a subject the composition of claim 9;

and

permitting the nanoparticles of said composition to locate in said blood clot,

whereby said radionuclide is delivered to said blood clot.

18. The method of claim 17, which further comprises imaging the blood clot by emissions from said radionuclide.

19. A method to obtain an ultrasound image of a blood clot which method comprises administering to a subject the composition of claim 1;

permitting the nanoparticles of said composition to locate in said blood clot; and

obtaining an ultrasound image of said blood clot.