IP Library Granted Patent US 11,504,437
Granted Patent B2
US 11,504,437 · App. 15/706,429 · Granted Nov 22, 2022

Multifunctional fluorescent and MRI-active nanostructure

Inventors: Nancy J. Halas (Houston, TX); Ciceron Ayala-Orozco (Stafford, TX); Sandra Bishnoi (Houston, TX); Luke Henderson (Houston, TX); Oara Neumann (Houston, TX); Robia Pautler (Houston, TX); Peter Nordlander (Houston, TX)
Assignees: WILLIAM MARSH RICE UNIVERSITY; BAYLOR COLLEGE OF MEDICINE
A61K49/1881A61K49/1833C23C18/1646C23C18/31H01B3/02
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Quick Facts
Patent No.
US 11,504,437
App. No.
15/706,429
Granted
Nov 22, 2022
Kind
B2
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.

Claims (44)

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.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 7, 2018
From: NORDLANDER, PETER
To: WILLIAM MARSH RICE UNIVERSITY
Reel/Frame 046812/0837 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 7, 2018
From: PAUTLER, ROBIA
To: BAYLOR COLLEGE OF MEDICINE
Reel/Frame 046812/0857 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 12, 2018
From: HALAS, NANCY J.; AYALA-OROZCO, CICERON; BISHNOI, SANDRA; HENDERSON, LUKE; NEUMANN, OARA
To: WILLIAM MARSH RICE UNIVERSITY
Reel/Frame 046055/0644 →
CONFIRMATORY LICENSE Recorded Oct 4, 2017
From: RICE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 043778/0719 →
Continuity (4)
Continuation In Part 14823891 · Aug 11, 2015
Provisional Application 62395188 · Sep 15, 2016
Provisional Application 62035716 · Aug 11, 2014
Related Publication 20180008730A1 · Jan 11, 2018