Lanthanide rich nanoparticles, and their investigative uses in MRI and related technologies
An aqueous soluble, lanthanide rich nanoparticle for investigative use, such as NMR, MRI, CT, PET, and GdNCT is provided. The nanoparticle is synthesized from a mixture comprising lanthanide ions and coated with a suitably selected organic ligand such that the resultant nanoparticle is soluble in aqueous solutions. A method of collecting nuclear magnetic resonance information on a sample or a subject is also provided.
1. An aqueous-soluble, lanthanide-rich nanoparticle composite, comprising:
an inorganic, paramagnetic core consisting of at least one lanthanide ion selected from ions of Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, La, Lu, Y, and combinations thereof, and at least one anion selected from a halide, a phosphate, and a vanadate;
at least one aqueous-soluble, organic ligand selected from citrate, biotin, amino acids, H 3 N + CH 2 CH 2 OPO 3 2− , and combinations thereof, wherein the at least one aqueous-soluble, organic ligand is bound to the inorganic, paramagnetic core; and
at least one surface-modifying reagent that has been reacted with the at least one aqueous-soluble, organic ligand to form a surface-modifying reagent-aqueous soluble organic ligand reaction product.
2. The nanoparticle of claim 1 wherein said inorganic, paramagnetic core consists of at least two lanthanide ions.
3. The nanoparticle of claim 2 wherein said at least two lanthanide ions are Gd 3+ and La 3+ .
4. The nanoparticle of claim 3 wherein said inorganic, paramagnetic core comprises gadolinium fluoride and lanthanum fluoride.
5. The nanoparticle of claim 4 wherein said inorganic, paramagnetic core comprises at least 50% gadolinium fluoride.
6. The nanoparticle of claim 5 wherein said inorganic, paramagnetic core comprises at least 80% gadolinium fluoride.
7. The nanoparticle composite of claim 1 wherein said at least one aqueous-soluble, organic ligand is either citrate or H 3 N + CH 2 CH 2 OPO 3 2− .
8. The nanoparticle of claim 7 wherein said inorganic, paramagnetic core consists of gadolinium fluoride and lanthanum fluoride.
9. The nanoparticle composite of claim 1 wherein the at least one lanthanide ion is selected from ions of Eu, Gd, Ho, and Er.
10. The nanoparticle composite of claim 9 wherein said at least one lanthanide ion is a gadolinium ion.
11. The nanoparticle composite of claim 10 wherein said at least one lanthanide ion is provided as gadolinium fluoride.
12. The nanoparticle composite of claim 11 wherein said at least one aqueous-soluble, organic ligand is citrate or H 3 N + CH 2 CH 2 OPO 3 2− .
13. The nanoparticle composite of claim 7 wherein said nanoparticle composite ranges in size from about 10 nm to about 150 nm in diameter.
14. The nanoparticle composite of claim 13 wherein said nanoparticle composite ranges in size from about 10 nm to about 20 nm.
15. The nanoparticle of claim 7 wherein said at least one aqueous-soluble, organic ligand is citrate.
16. The nanoparticle composite of claim 15 wherein said nanoparticle composite ranges in size from about 5 nm to about 10 nm.
17. The nanoparticle composite of claim 1 wherein said nanoparticle composite is a core shell nanoparticle.
18. The core shell nanoparticles of claim 17 wherein said nanoparticles consists of GdF 3 :Eu(5%)-LaF 3 or LaF 3 —Gd:Eu(5%).
19. The nanoparticle composite of claim 1 wherein said nanoparticle composite is a core nanoparticle.
20. An aqueous-soluble, lanthanide-rich nanoparticle composite, comprising:
an inorganic, paramagnetic core consisting of at least one lanthanide ion selected from ions of Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, La, Lu, Y, and combinations thereof, and at least one anion selected from a halide, a phosphate, and a vanadate;
at least one H 3 N + CH 2 CH 2 OPO 3 2− ligand, wherein the at least one H 3 N + CH 2 CH 2 OPO 3 2− ligand is bound to the inorganic, paramagnetic core; and
at least one surface-modifying reagent selected from an activated ester, a polyethylene glycol, a peptide, an antibody, and combinations thereof, wherein the at least one surface- modifying reagent is bound to the at least one H 3 N + CH 2 CH 2 OPO 3 2− ligand through an amine of the H 3 N + CH 2 CH 2 OPO 3 2− ligand.
21. An aqueous-soluble, lanthanide-rich nanoparticle composite, consisting of:
an inorganic, paramagnetic core consisting of at least one lanthanide ion selected from ions of Eu, Gd, Dy, Ho, Er, La, Lu, Y, and combinations thereof, and at least one anion selected from a halide, a phosphate, and a vanadate;
at least one citrate ligand bound to the inorganic, paramagnetic core; and
at least one antibody that has been reacted with the at least one citrate ligand to form an antibody-citrate ligand reaction product useful for targeting the nanoparticle for a desired NMR, MRI, CT, PET, or NCT application.
22. The nanoparticle composite of claim 1 wherein the at least one surface-modifying reagent is selected from a reagent capable of detecting a target, a non- biological polymer, and combinations thereof.
23. The nanoparticle composite of claim 1 wherein the at least one surface-modifying reagent is selected from an activated ester, a polyethylene glycol, a peptide, an antibody, and any combinations thereof.
24. An aqueous-soluble, lanthanide-rich nanoparticle composite, comprising:
GdF 3 core;
at least one citrate ligand bound to the GdF 3 core; and
at least one antibody that has been reacted with the at least one citrate ligand to form an antibody-citrate ligand reaction product useful for targeting the nanoparticle for a desired NMR, MRI, CT, PET, or NCT application.