Fluorescent magnetic nanoprobes, methods of making, and methods of use

Patent metadata

Field	Value
Publication number	US-9402926-B2
Application number	US-201414255210-A
Country	US
Kind code	B2
Filing date	Apr 17, 2014
Priority date	Jul 10, 2008
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

Abstract

Embodiments of the present disclosure provide for nanoprobes, methods of imaging, methods of imaging a target, methods of making nanoprobes, and the like.

First claim

We claim the following:

1. A nanoprobe, comprising:
a superparamagnetic iron oxide (SPIO) nanoparticle, wherein the SPIO nanoparticle has a silanization coating on the surface of the SPIO nanoparticle, wherein the silanization coating is about 5 to about 1000 nm thick, or more, does not include silicates or silica, and is made of cross-linked trimethoxyl silanes that are cross-linked with two or more different types of functional groups, wherein the functional groups are selected from the group consisting of: an amino group, a mercapto group, a carboxyl group, a phosphonate group, a polyethylene oxide group (PEG), a hydroxyl group, an alkyl group and a combination thereof.

2. The nanoprobe of claim 1 , further comprising at least ten fluorescent compounds attached to the silanization coating.

3. The nanoprobe of claim 1 , wherein the SPIO nanoparticle has a diameter of about 3 nm to 40 nm.

4. The nanoprobe of claim 1 , wherein silanization coating is amorphous and controllable to about 5 nm to 500 nm thick.

5. The nanoprobe of claim 1 , wherein the SPIO nanoparticle is a product of an oxidative decomposition of iron pentacarbonyl with a compound selected from the group consisting of: trimethylamine oxide, oleic acid, hexadecane, and a combination thereof.

6. The nanoprobe of claim 2 , wherein the fluorescent compounds are attached to the silanization coating through an interaction selected from the group consisting of: covalent bond, a non-covalent bond, an ionic bond, a chelation interaction, a hydrophobic interaction, a hydrophilic interaction, a charge-charge interaction, and a π-stacking interaction.

7. The nanoprobe of claim 1 , wherein the SPIO nanoparticles are precipitated with isopropanol prior to silanization.

8. The nanoprobe of claim 2 , wherein the fluorescent compounds are attached to the silanization coating via at least one of the types of functional group.

9. The nanoprobe of claim 1 , wherein the silanization coating includes biotin.

10. The nanoprobe of claim 9 , wherein a streptavidin-fluorescent compound is attached to the silanization coating via biotin.

11. The nanoprobe of claim 1 , wherein a targeting moiety is attached to the silanization coating, wherein the targeting moiety has an affinity for a target.

12. The nanoprobe of claim 2 , wherein the fluorescent compound is a fluorophore.

13. The nanoprobe of claim 1 , wherein the iron oxide nanoparticle comprises one or more particles composed of a phase selected from the group consisting of: a maghemite ((γ-Fe 2 O 3 ) phase, a magnetite (Fe 3 O 4 ) phase, and a combination of both phases.

14. The nanoprobe of claim 1 , wherein at least one type of fluorescent compound is attached to one type of functional group; and at least one second type of compound is attached to the other type of functional group, wherein the second type of compound is selected from: a second type of fluorescent compound, a targeting moiety, a drug, a therapeutic agent, a radiological agent, a chemological agent, a small molecule drug, and a biological agent.

15. The nanoprobe of claim 1 , wherein the silanization coating does not change the magnetic properties of the original SPIO nanoparticle.

16. The nanoprobe of claim 1 , wherein the silanization coating includes amino functional groups and mercapto functional groups.

17. The nanoprobe of claim 16 , wherein a portion of the amino functional groups are attached to fluorescent compounds, where each amino functional group of the portion is attached to a fluorescent compound; and a portion of the mercapto functional groups are attached to targeting moieties, wherein each mercapto functional group of the portion is attached to a targeting moiety.

18. A nanoprobe, comprising:
a superparamagnetic iron oxide (SPIO) nanoparticle, wherein the SPIO nanoparticle has a silanization coating on the surface of the SPIO nanoparticle, wherein the silanization coating is about 5 nm to 1000 nm thick, does not include silicates or silica, and includes two or more different functional groups, wherein the functional groups are selected from the group consisting of: an amino group, a mercapto group, a carboxyl group, a phosphonate group, a polyethylene oxide group (PEG), a hydroxyl group, an alkyl group and a combination thereof, and
at least ten fluorescent compounds attached to the functional groups of the silanization coating, wherein each fluorescent compound is attached to the silanization coating via a functional group, and wherein the silanization coating provides a protective effect for the fluorescent compound.

Assignees

• Univ Leland Stanford Junior

Inventors

• Fu Aihua
• Wang Shan X
• Gambhir Sanjiv S

Classifications

• A61K49/1866

  the nanoparticle having a (super)(para)magnetic core coated or functionalised with a peptide, e.g. protein, polyamino acid · CPC title

• A61K51/1244 Primary

  microparticles or nanoparticles, e.g. polymeric nanoparticles · CPC title

• A61K49/0045

  the fluorescent agent being a peptide or protein used for imaging or diagnosis in vivo · CPC title

• A61K49/005

  characterised by the carrier molecule carrying the fluorescent agent · CPC title

• A61K9/5094

  Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting · CPC title