Rod-shaped plant virus nanoparticles as imaging agent platforms

Patent metadata

Field	Value
Publication number	US-10086095-B2
Application number	US-201314434435-A
Country	US
Kind code	B2
Filing date	Oct 9, 2013
Priority date	Oct 9, 2012
Publication date	Oct 2, 2018
Grant date	Oct 2, 2018

Abstract

A rod-shaped plant virus having an interior surface and an exterior surface, and at least one imaging agent that is linked to the interior and/or exterior surface is described. The rod-shaped viruses can be combined into larger spherical nanoparticles. A rod-shaped plant virus or spherical nanoparticles including an imaging agent can be used in a method of generating an image of a tissue region of a subject such as a tumor or atherosclerotic tissue by administering the virus particle to the subject and generating an image of the tissue region of the subject to which the virus particle has been distributed.

First claim

What is claimed is:

1. A rod-shaped plant virus having an interior surface and an exterior surface, and at least one imaging agent that is linked to the interior and/or exterior surface of the virus, wherein the virus has a longitudinal relaxivity of greater than about 10 mM −1 S −1 per linked imaging agent at 60 mHz.

2. The rod-shaped plant virus of claim 1 , wherein the imaging agent is a magnetic resonance imaging agent.

3. The rod-shaped plant virus of claim 1 , wherein the imaging agent is a chelated lanthanide.

4. The rod-shaped plant virus of claim 3 , wherein the lanthanide is gadolinium.

5. The rod-shaped plant virus of claim 1 , wherein the imaging agent is linked to the interior and the exterior of the virus.

6. The rod-shaped plant virus of claim 1 , wherein a first imaging agent is linked to the interior of the virus and a second, different imaging agent is linked to the exterior of the virus.

7. The rod-shaped plant virus of claim 1 , wherein a targeting moiety is linked to the exterior surface of the virus.

8. The rod-shaped plant virus of claim 1 , wherein the rod-shaped virus is PEGylated.

9. The rod-shaped plant virus of claim 1 , wherein at least about 3000 imaging agent molecules are linked to the virus particle.

10. The rod-shaped plant virus of claim 1 , wherein the plant virus belongs to the Virgaviridae family.

11. The rod-shaped plant virus of claim 1 , wherein the virus is a tobacco mosaic virus.

12. The rod-shaped plant virus of claim 1 , wherein the virus has a longitudinal relaxivity of greater than about 10 mM −1 S −1 per particle when measured at 60 mHz at a physiological pH.

13. A method of generating an image of a tissue region of a subject, by administering to the subject a diagnostically effective amount of a rod-shaped plant virus particle having an imaging agent linked to an interior and/or exterior surface of the virus particle, and generating an image of the tissue region of the subject to which the rod-shaped plant virus particle has been distributed.

14. The method of claim 13 , wherein the rod-shaped plant virus is a tobacco mosaic virus.

15. The method of claim 13 , wherein the method of generating an image is magnetic resonance imaging, and the imaging agent is a chelated lanthanide.

16. The method of claim 13 , wherein the rod-shaped plant virus particle is administered together with a pharmaceutically acceptable carrier.

17. The method of claim 13 , wherein the tissue region includes a tumor.

18. The method of claim 13 , wherein the tissue region includes a blood vessel.

Assignees

• Univ Case Western Reserve

Inventors

• Steinmetz Nicole
• Bruckman Michael

Classifications

• A61K49/1884

  Nanotubes, nanorods or nanowires · CPC title

• C12N2770/00031

  Uses of virus other than therapeutic or vaccine, e.g. disinfectant · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• A61K49/1896 Primary

  not provided for elsewhere, e.g. cells, viruses, ghosts, red blood cells, virus capsides · CPC title