IP Library Granted Patent US 10,232,059
Granted Patent B2
US 10,232,059 · App. 14/977,366 · Granted Mar 19, 2019

Functionalized magnetic nanoparticles and use in imaging amyloid deposits and neurofibrillary tangles

Inventor: Massoud Akhtari (Pasadena, CA)
Assignee: The Regents of the University of California
A61K49/10A61K9/0019A61K31/132A61K31/133A61K31/136A61K31/145A61K31/167A61K31/277A61K31/427A61K31/428A61K31/44A61K31/444A61K31/4439A61K31/472A61K31/4745A61K49/1833
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Quick Facts
Patent No.
US 10,232,059
App. No.
14/977,366
Granted
Mar 19, 2019
Kind
B2
Abstract

The present disclosure provides functionalized magnetic nanoparticles (MNPs) comprising a functional group that binds to β-amyloid deposits and/or neurofibrillary tangles. The present disclosure provides compositions comprising the functionalized MNPs, and methods of using the functionalized MNPs in imaging β-amyloid deposits and neurofibrillary tangles.

Claims (25)

1. A pharmaceutical composition comprising:

a) a functionalized magnetic nanoparticle (MNP) comprising a magnetic core and a functional group that binds aggregated β-amyloid protein and/or neurofibrillary tangles, wherein said functional group is coupled via a linker to the magnetic core, wherein said functionalized magnetic nanoparticle is capable, when introduced into the bloodstream of a mammalian subject, of crossing the blood-brain barrier of a mammalian subject;

wherein the functional group is coupled via a hydroxyl moiety, a primary amine moiety or a thiol moiety directly or indirectly to the linker; and

wherein the functional group is selected from:

b) a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1 , wherein the functionalized magnetic nanoparticle (MNP) of the formula:

M-S-(L)-Z, wherein M is a magnetic core, S is a polymer, L is the linker, and Z is the functional group.

3. The pharmaceutical composition of claim 2 , wherein the polymer is dextran.

4. The pharmaceutical composition of claim 2 , wherein the polymer is an epoxysilane.

5. The pharmaceutical composition of claim 1 , wherein the functional group is coupled to the magnetic core via an epoxy group.

6. The pharmaceutical composition of claim 1 , wherein the functionalized MNP further comprises a therapeutic agent.

7. The pharmaceutical composition of claim 1 , wherein the functionalized MNP is encapsulated in an albumin matrix.

8. The pharmaceutical composition of claim 1 , wherein the functionalized MNP comprises an apolipoprotein.

9. The pharmaceutical composition of claim 1 , wherein the functionalized MNP comprises poly(butyl cyanoacrylate) (PBCA).

10. The pharmaceutical composition of claim 1 , wherein the functionalized MNP comprises a surfactant.

11. The pharmaceutical composition of claim 10 , wherein the surfactant is selected from polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, and polyoxyethylene sorbitan monolaurate.

12. The pharmaceutical composition of claim 10 , wherein the surfactant is a block copolymer of polyethylene oxide and polypropylene oxide.

13. The pharmaceutical composition of claim 10 , wherein the functionalized MNP comprises a poloxamine.

14. A method for detecting Alzheimer's Disease or a predisposition thereto in the brain of a live mammal, the method comprising: a) administering to the mammal a diagnostically effective amount of the pharmaceutical composition of claim 1 ; b) allowing the functionalized MNP to distribute into the brain tissue; and c) imaging the brain tissue via magnetic resonance imaging, wherein an increase in binding of the functionalized MNP to the brain tissue compared to a normal control level of binding indicates that the mammal is suffering from or is at risk of developing Alzheimer's Disease.

15. The method of claim 14 , wherein the composition is administered by intravenous injection.

16. The method of claim 14 , wherein the live mammal is a human.

17. A method for detecting β-amyloid deposits and/or neurofibrillary tangles in the brain of a live mammal, the method comprising: a) administering to the mammal a diagnostically effective amount of the pharmaceutical composition of claim 1 ; b) allowing the functionalized MNP to distribute into the brain tissue; and c) imaging the brain tissue via magnetic resonance imaging, wherein an increase in binding of the functionalized MNP to the brain tissue compared to a normal control level of binding indicates the presence of β-amyloid deposits and/or neurofibrillary tangles in the brain.

18. The method of claim 17 , wherein the composition is administered by intravenous injection.

19. The method of claim 17 , wherein the live mammal is a human.

20. The method of claim 17 , wherein the live mammal is a non-human animal model of a disease associated with β-amyloid deposits and/or neurofibrillary tangles.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 16, 2016
From: AKHTARI, MASSOUD
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 038004/0639 →
Continuity (3)
Division 14007298
Provisional Application 61477958 · Apr 21, 2011
Related Publication 20160184461A1 · Jun 30, 2016