Functionalized magnetic nanoparticles and use in imaging amyloid deposits and neurofibrillary tangles
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.
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, and wherein the functional group is (4′-aminophenyl)-6-hydroxybenzothiazole (PIB-2), or a derivative or analog thereof; and
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 an optional linker, and Z is the functional group.
3. The pharmaceutical composition of claim 2 , wherein the functional group is attached to the polymer directly or via a linker.
4. The pharmaceutical composition of claim 1 , wherein the functional group is coupled to the magnetic core via an epoxy group.
5. The pharmaceutical composition of claim 1 , wherein the PIB-2 functional group is coupled to the magnetic core via the amino nitrogen group of PIB-2.
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. The pharmaceutical composition of claim 2 , wherein the polymer is dextran.
15. 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.
16. The method of claim 15 , wherein the composition is administered by intravenous injection.
17. The method of claim 15 , wherein the live mammal is a human.
18. 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.
19. The method of claim 18 , wherein the composition is administered by intravenous injection.
20. The method of claim 18 , wherein the live mammal is a human.
21. The method of claim 18 , wherein the live mammal is a non-human animal model of a disease associated with β-amyloid deposits and/or neurofibrillary tangles.