Coated plant virus imaging agents

Patent metadata

Field	Value
Publication number	US-11730833-B2
Application number	US-202117522182-A
Country	US
Kind code	B2
Filing date	Nov 9, 2021
Priority date	Aug 5, 2014
Publication date	Aug 22, 2023
Grant date	Aug 22, 2023

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. An imaging nanoparticle, comprising a tobacco mosaic virus particle having an interior surface and an exterior surface, a chelated lanthanide imaging agent that is linked to the exterior surface, and a layer of silica coated over the exterior surface, wherein the tobacco mosaic virus particle is selected from the group consisting of iGd-TMV-Si, eGd-TMV, eGd-TMV-Si, Gd-SNP, and Gd-SNP-Si, and wherein the tobacco mosaic virus particle has a relaxivity of greater than about 25,000 mM −1 S −1 per particle.

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

3. The imaging nanoparticle of claim 2 , wherein the targeting moiety binds specifically to an immune cell.

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

5. The method of claim 1 , wherein the silica maintains the ionic relaxivity of the particles compared to the ionic relaxivity of a non-siliconized particle.

6. The method of claim 1 , wherein the silica reduces the immunogenicity of the particles when administered to a subject compared to a non-siliconized particle.

7. A 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, comprising a tobacco mosaic virus particle having an interior surface and an exterior surface, a chelated lanthanide imaging agent that is linked to the exterior surface, and a layer of silica coated over the exterior surface, wherein the tobacco mosaic virus particle is selected from the group consisting of iGd-TMV-Si, eGd-TMV, eGd-TMV-Si, Gd-SNP, and Gd-SNP-Si, and wherein the tobacco mosaic virus particle has a relaxivity of greater than about 25,000 mM −1 S −1 per particle, and generating an image of the tissue region of the subject to which the imaging nanoparticle has been distributed.

8. The method of claim 7 , wherein the method of generating an image is magnetic resonance imaging.

9. The method of claim 7 , wherein the imaging nanoparticle further comprises a targeting moiety is linked to the exterior surface of the virus particle.

10. The method of claim 9 , wherein the targeting moiety specifically binds to an immune cell.

11. The method of claim 7 , wherein the tissue region includes a blood vessel.

12. The method of claim 7 , wherein the silica maintains the ionic relaxivity of the particles compared to the ionic relaxivity of a non-mineralized particle.

13. The method of claim 7 , wherein the silicon reduces the immunogenicity of the particles when administered to the subject compared to a non-siliconized particle.

Assignees

• Univ Case Western Reserve
• Case Western Univ

Inventors

• Steinmetz Nicole F
• Bruckman Michael
• Randolph Lauren

Classifications

• A61K49/1896 Primary

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

• A61K49/085

  conjugated systems · CPC title

• A61K49/108

  the metal complex being Gd-DOTA · CPC title