Coated plant virus imaging agents

Patent metadata

Field	Value
Publication number	US-10207014-B2
Application number	US-201815937681-A
Country	US
Kind code	B2
Filing date	Mar 27, 2018
Priority date	Aug 5, 2014
Publication date	Feb 19, 2019
Grant date	Feb 19, 2019

Abstract

An imaging nanoparticle comprising a plant virus particle having an interior surface and an exterior surface, an imaging agent that is linked to the interior and/or exterior surface, and a layer of biocompatible mineral such as silica coated over the exterior surface, is described. The imaging nanoparticle can be used in method of generating an image of a tissue region of a subject, by administering to the subject a diagnostically effective amount of an imaging nanoparticle and generating an image of the tissue region of the subject to which the imaging nanoparticle has been distributed.

First claim

What is claimed is:

1. A spherical imaging nanoparticle, comprising a spherical arrangement of a plurality of rod-shaped plant virus particles, each rod-shaped plant particle having an interior surface, and an imaging agent that is linked to the interior surface, and a biocompatible mineral coating on an exterior surface of the spherical arrangement of rod-shaped plant virus particles.

2. The imaging nanoparticle of claim 1 , wherein the biocompatible mineral is silica.

3. The imaging nanoparticle of claim 1 , wherein the spherical arrangement is formed from coat proteins of the rod-shaped virus particles.

4. The imaging nanoparticle of claim 3 , wherein the rod-shaped virus particles belong to the Virgaviridae family.

5. The imaging nanoparticle of claim 3 , wherein the rod-shaped virus particles are tobacco mosaic virus particles.

6. The imaging nanoparticle of claim 1 , wherein the imaging agent is a magnetic resonance imaging agent.

7. The imaging nanoparticle of claim 6 , wherein the imaging agent is a chelated lanthanide.

8. The imaging nanoparticle of claim 7 , wherein the lanthanide is gadolinium.

9. The imaging nanoparticle of claim 8 , wherein the plant virus particles are selected from the group consisting of iGd-TMV-Si, eGd-TMV, eGd-TMV-Si, Gd-SNP, and Gd-SNP-Si, and wherein the plant virus particles have a relaxivity of greater than about 25,000 mM −1 S −1 per particle.

10. The imaging nanoparticle of claim 1 , wherein a targeting moiety is linked to the exterior surface of the virus particle.

11. The imaging nanoparticle of claim 1 , wherein at least about 500 imaging agent molecules are linked to the virus particle.

12. The spherical imaging nanoparticle of claim 1 , the spherical arrangement of a plurality of rod-shaped plant virus particles is formed from about 10 to about 50 rod-shaped virus particles.

13. A method of generating an image of a tissue region of a subject, the method comprising administering to the subject a diagnostically effective amount of an imaging nanoparticle, comprising a spherical arrangement of a plurality of rod-shaped plant virus particles, each rod-shaped plant virus particle having an interior surface and an imaging agent that is linked to the interior surface, and a layer of biocompatible mineral coating an exterior surface of the spherical arrangement of rod-shaped plant virus particles, and generating an image of the tissue region of the subject to which the imaging nanoparticle has been distributed.

14. The method of claim 13 , wherein the biocompatible mineral is silica.

15. The method of claim 13 , wherein the spherical plant virus is formed from coat proteins of a rod-shaped virus particles.

16. The method of claim 15 , wherein the rod shaped virus particles are tobacco mosaic virus particles.

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

18. The method of claim 13 , wherein the imaging nanoparticle further comprises a targeting moiety is linked to the exterior surface of the virus particle.

19. The method of claim 13 , the spherical arrangement of a plurality of rod-shaped plant virus particles is formed from about 10 to about 50 rod-shaped virus particles.

Assignees

• Case Wester Reserve Univ
• Univ Case Western Reserve

Inventors

• Steinmetz Nicole F
• Bruckman Michael
• Randolph Lauren

Classifications

• A61K49/108

  the metal complex being Gd-DOTA · CPC title

• A61K49/085

  conjugated systems · CPC title

• A61K49/1896 Primary

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