Method of preparing iron oxide nanoparticles coated with hydrophilic material, and magnetic resonance imaging contrast agent using the same
The present invention relates to a method of preparing biocompatible iron oxide nanoparticles by coating iron oxide nanoparticles having improved magnetism via annealing treatment using salt particles with a hydrophilic material and to a magnetic resonance imaging (MRI) contrast agent including the iron oxide nanoparticles prepared thereby. Among hydrophilic materials, carboxymethyl dextran (CM-dextran) is the most efficient in terms of stabilizing the annealed iron oxide nanoparticles and exhibiting contrast effects.
1. A method of preparing iron oxide nanoparticles coated with a hydrophilic material, comprising:
a) annealing a power mixture comprising salt particles and magnetic iron oxide nanoparticles coated with a hydrophobic organic material, thus obtaining iron oxide nanoparticles having no organic material; and
b) coating a surface of the iron oxide nanoparticles having no organic material with a hydrophilic material,
wherein the annealing in a) is performed under air conditions.
2. The method of claim 1 , wherein the hydrophobic organic material coated to the iron oxide nanoparticles in a) is at least one selected from the group consisting of a C 4 ˜C 25 fatty acid, a C 4 ˜C 25 aliphatic alcohol, and a C 4 ˜C 25 aliphatic amine.
3. The method of claim 2 , wherein the fatty acid is oleic acid.
4. The method of claim 1 , wherein the salt particles in a) is at least one selected from the group consisting of sodium sulfate (Na 2 SO 4 ), sodium bicarbonate (NaHCO 3 ), potassium bicarbonate (KHCO 3 ), calcium bicarbonate (Ca(HCO 3 ) 2 ), sodium chloride (NaCl), potassium chloride (KCl) and calcium chloride (CaCl 2 ).
5. The method of claim 1 , wherein the salt particles in a) have a diameter of 1˜500 μm.
6. The method of claim 1 , wherein the magnetic iron oxide nanoparticles in a) are obtained by reacting an iron complex comprising iron as a center atom and a C 4 ˜C 25 organic acid group (carboxylate) attached thereto as a ligand with a C 4 ˜C 25 fatty acid.
7. The method of claim 6 , wherein the iron complex is iron oleate.
8. The method of claim 6 , wherein the fatty acid is oleic acid.
9. The method of claim 1 , wherein the magnetic iron oxide nanoparticles in a) have a diameter of 1˜100 nm.
10. The method of claim 1 , wherein the magnetic iron oxide nanoparticles and the salt particles in a) have a weight ratio ranging from 1:10 to 1:1000.
11. The method of claim 1 , wherein the annealing in a) is performed by carrying out heating at 400˜600° C. for 1˜10 hr in an air atmosphere.
12. The method of claim 1 , wherein, after annealing in a), removing the salt particles is additionally performed.
13. The method of claim 12 , wherein the removing the salt is performed using centrifugation.
14. The method of claim 12 , wherein the temperature is decreased to room temperature before the removing the salt after annealing in a).
15. The method of claim 1 , wherein the hydrophilic material in b) is a dextran derivative, polyacrylic acid, starch, silica, polyethyleneglycol (PEG) or PEG-phosphate (PO-PEGs).
16. The method of claim 15 , wherein the dextran derivative is diethylaminoethyl-dextran (DEAE-dextran), dextran sulfate (DS) or carboxymethyl dextran (CM-dextran).
17. The method of claim 1 , wherein removing the salt are simultaneously performed with the coating in b).