Magnetic nanoparticles for disease diagnostics
Provided herein is a nanoparticle comprising a metal core and a polymer shell coating the metal core useful as a magnetic resonance contrast agent.
1. A nanoparticle comprising a metal core and a polymer shell coating the metal core, wherein the polymer shell comprises an inner shell comprising a first polymer and an outer shell comprising a second polymer, wherein the first polymer comprises a polyethylene glycol: polylactic acid coblock polymer (PEG-PLA) or a polyethylene glycol: poly(lactic-co-glycolic acid) coblock polymer (PEG:PLGA) and the second polymer is polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), a polyamide, or a combination thereof and the mass ratio of the metal core to the first polymer to the second polymer is about 1:0.25:3 to about 1:4:4.
2. The nanoparticle of claim 1 , wherein the metal core comprises Fe, Gd, Mn, Sn, Zn, Cu, Mg, or Pt.
3. The nanoparticle of claim 2 , wherein the metal core comprises a metal flavonoid salt, a metal curcumonoid salt or a metal dye salt.
4. The nanoparticle of claim 3 , wherein the metal curcumonoid salt comprises curcumin, demethoxycurcumin, or bismthoxycurcumin and the metal dye salt comprises di sodium 4-amino-3-[4-[4-(1-amino-4-sulfonato-naphthalen-2-yl)diazenylphenyl]phenyl]diazenyl-naphthalene-1-sulfonate, Thioflavin T, or Thioflavin S.
5. The nanoparticle of claim 2 , wherein the metal core comprises Fe, Gd, Mn, or Sn.
6. The nanoparticle of claim 2 , wherein the metal core comprises FeO 3, a core-shell Fe(0)@Fe 3 O 4 , or Fe(Cur) 3 .
7. The nanoparticle of claim 1 , wherein the first polymer is PEG-PLA comprising a polyethylene glycol block having an average molecular weight of 1,000 to 15,000 amu and a polylactic acid block having an average molecular weight of 1,000 to 15,000 amu.
8. The nanoparticle of claim 4 , wherein the first polymer is PEG-PLA comprising a polyethylene glycol block having an average molecular weight of 1,000 to 3,000 amu and a polylactic acid block having an average molecular weight of 7,000 to 10,000 amu.
9. The nanoparticle of claim 1 , wherein the first polymer is PEG:PLGA comprising a polyethylene glycol block having an average molecular weight of 1,000 to 15,000 amu and poly(lactic-co-glycolic acid) block having an average molecular weight of 1,000 to 15,000 amu.
10. The nanoparticle of claim 8 , wherein the second polymer is PVP having an average molecular weight of 12,000 to 30,000.
11. The nanoparticle of claim 10 , wherein the metal core comprises Fe(Cur) 3 and the mass ratio of the metal core to the first polymer to the second polymer is about 1:0.5:3.4 to about 1:3:3.8.
12. The nanoparticle of claim 11 , wherein the first polymer is PEG-PLA comprising a polyethylene glycol block having an average molecular weight of 2,000 amu and a polylactic acid block having an average molecular weight of 10,000 amu.
13. The nanoparticle of claim 12 , wherein the average hydrodynamic diameter of the nanoparticle is about 10 nm to about 300 nm.
14. A pharmaceutical composition comprising a diagnostically effective amount of a nanoparticle of claim 1 and at least one pharmaceutically acceptable excipient.
15. A method of performing a magnetic resonance imaging diagnostic procedure comprising the steps of:
a. administering to a subject a diagnostically effective amount of a nanoparticle of claim 1 ; and
b. exposing the subject to a magnetic resonance imaging procedure, thereby generating an image of at least a portion of the body of the subject.
16. The method of claim 15 , wherein the nanoparticle comprises a metal flavonoid salt that binds to amyloid plaques in the subject.
17. The method of claim 15 , further comprising the step of processing the image of at least a portion of the body of the subject to diagnose the presence or absence of Alzheimer's disease, Huntington's disease, mad cow disease, multiple sclerosis, Parkinson's disease, Lewy body dementia, or stroke.
18. The method of claim 16 , wherein the at least a portion of the body of the subject comprises the brain.
19. The method of claim 15 , wherein the subject is a human.
20. The method of claim 15 , wherein the nanoparticle of claim 1 is administered parentally.