Multifunctional fluorescent and MRI-active nanostructure

Patent metadata

Field	Value
Publication number	US-11504437-B2
Application number	US-201715706429-A
Country	US
Kind code	B2
Filing date	Sep 15, 2017
Priority date	Aug 11, 2014
Publication date	Nov 22, 2022
Grant date	Nov 22, 2022

Abstract

A Magnetic Resonance Imaging (MRI) enhancement agent includes a plurality of particles, each particle including: a metal core; a dielectric shell disposed on the metal core comprising at least one MRI contrast agent; and a metal shell disposed on the exterior surface of the dielectric shell that encapsulates the dielectric shell.

First claim

What is claimed is:

1. A Magnetic Resonance Imaging (MRI) enhancement agent, comprising:
a plurality of particles, each particle comprising:
a metal core, wherein a radius of the metal core is between about 5 nm and 60 nm;
a dielectric shell disposed on the metal core, the dielectric shell comprising:
a dielectric material;
a fluorescing, phosphorescent, or luminescent material loaded in a middle portion of the dielectric shell along a thickness of the dielectric shell; and
at least one MRI contrast agent comprising a type 1 contrast agent, wherein the type 1 contrast agent is a chelated metal ion; and

a metal shell disposed on the exterior surface of the dielectric shell that encapsulates the dielectric shell, wherein the metal shell is the outermost layer of the particle.

2. The magnetic resonance imaging enhancement agent of claim 1 , wherein the thickness of the dielectric shell is between about 5 and 40 nm.

3. The magnetic resonance imaging enhancement agent of claim 1 , wherein a thickness of the metal shell is between 1 and 100 nm.

4. The magnetic resonance imaging enhancement agent of claim 1 , wherein at least a portion of the plurality of particles supports a plasmon resonance centered at greater than 400 nm and less than 1200 nm.

5. The magnetic resonance imaging enhancement agent of claim 1 , wherein the dielectric material is amorphous silica.

6. The magnetic resonance imaging enhancement agent of claim 1 , wherein the at least one MRI contrast agent further comprises a type 2 contrast agent, wherein the type 2 contrast agent is iron oxide.

7. The magnetic resonance imaging enhancement agent of claim 1 , wherein the chelate is selected from diethylene triamine pentaacetic acid or 2-(4-Isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10 tetra acetic acid.

8. The magnetic resonance imaging enhancement agent of claim 1 , wherein the metal core is gold or silver.

9. The magnetic resonance imaging enhancement agent of claim 1 , wherein the metal shell is gold or silver.

10. The MRI enhancement agent of claim 1 , wherein the at least one MRI contrast agent has a diameter of less than 5 nm.

11. A method of producing the particles of claim 1 , comprising:
coating the metal core with the dielectric material to obtain a dielectric coating around the metal core;
loading the dielectric coating with the at least one MRI contrast agent and chemically bonding the chelated metal ion to the dielectric material to obtain the dielectric shell;
seeding the exterior surface of the dielectric shell with a metal to obtain a seeded dielectric shell; and
coating the seeded dielectric shell with a metal plating solution to obtain the metal shell that encapsulates the dielectric shell.

12. The method of claim 11 , wherein the dielectric is amorphous silica.

13. The method of claim 12 , wherein the amorphous silica is doped with an amine.

14. The method of claim 13 , wherein the amine is 3-aminopropyl-triethoxysilane.

15. The method of claim 11 , wherein the metal core is gold or silver.

16. The method of claim 11 , wherein the metal seeded on the dielectric is gold or silver.

17. A Magnetic Resonance Imaging (MRI) enhancement agent, comprising:
a plurality of particles, each particle comprising:
a metal core, wherein a radius of the metal core is between about 5 nm and 60 nm;
a dielectric shell disposed on the metal core, the dielectric shell comprising:
a dielectric material,
a fluorescing, phosphorescent, or luminescent material loaded in a middle portion of the dielectric shell along a thickness of the dielectric shell;
at least one MRI contrast agent; and
a chelate, wherein the at least one MRI contrast agent is chelated to the chelate; and

a metal shell disposed on the exterior surface of the dielectric shell that encapsulates the dielectric shell, wherein the metal shell is the outermost layer of the particle.

18. A Magnetic Resonance Imaging (MRI) enhancement agent, comprising:
a plurality of particles, each particle comprising:
a metal core;
a dielectric shell disposed on the metal core, the dielectric shell comprising:
silica;
at least one MRI contrast agent loaded in the silica, the at least one MRI contrast agent selected from a type 1 contrast agent, wherein the type 1 contrast agent is a chelated metal ion; and
a fluorescing, phosphorescent, or luminescent material loaded in a middle portion of the dielectric shell along a thickness of the dielectric shell; and

a metal shell disposed on the exterior surface of the dielectric shell that encapsulates the dielectric shell, wherein the metal shell is the outermost layer of the particle.

Assignees

• Univ Rice William M
• Baylor College Medicine

Inventors

• Halas Nancy J
• Ayala-Orozco Ciceron
• Bishnoi Sandra
• Henderson Luke
• Neumann Oara
• Pautler Robia
• Nordlander Peter

Classifications

• C23C18/31

  Coating with metals · CPC title

• A61K49/1833

  having a (super)(para)magnetic core coated or functionalised with a small organic molecule (oligomeric, polymeric, dendrimeric A61K49/1851) · CPC title

• H01B3/02

  mainly consisting of inorganic substances · CPC title

• A61K49/1881 Primary

  wherein the coating consists of chelates, i.e. chelating group complexing a (super)(para)magnetic ion, bound to the surface · CPC title

• C23C18/1646

  Characteristics of the product obtained · CPC title