Aqueous method for making magnetic iron oxide nanoparticles

• US 9,125,941 B2
• Filed: 06/25/2014
• Issued: 09/08/2015
• Est. Priority Date: 07/16/2007
• Status: Expired due to Fees

• Current Assignee: University of Central Florida Research Foundation Inc. (State University System of Florida)
• Original Assignee: University of Central Florida Research Foundation Inc. (State University System of Florida)
• Inventors: Perez, Jesus Manuel, Nath, Sudip
• Primary Examiner(s): ZISKA, SUZANNE E
• Application Number:
  US14/315,082
• Publication Number:
  US 20150023882A1
• Time in Patent Office: 440 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 49/1836 the small organic molecule being a carboxylic acid having less than 8 carbon atoms in the main chain
• CPC Class Codes: A61K 49/1848 the small organic molecule being a silane
• CPC Class Codes: A61K 49/1863 the organic macromolecular compound being a polysaccharide or derivative thereof, e.g. chitosan, chitin, cellulose, pectin, starch
• CPC Class Codes: A61K 49/1866 the nanoparticle having a (super)(para)magnetic core coated or functionalised with a peptide, e.g. protein, polyamino acid
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C01G 49/08 Ferroso-ferric oxide [Fe3O4]
• CPC Class Codes: C01P 2002/72 by d-values or two theta-values, e.g. as X-ray diagram
• CPC Class Codes: C01P 2002/85 by XPS, EDX or EDAX data
• CPC Class Codes: C01P 2004/04 obtained by TEM, STEM, STM or AFM
• CPC Class Codes: C01P 2004/16 Nanowires or nanorods, i.e. solid nanofibres with two nearly equal dimensions between 1-100 nanometer
• CPC Class Codes: C01P 2004/32 Spheres
• CPC Class Codes: C01P 2004/62 Submicrometer sized, i.e. from 0.1-1 micrometer
• CPC Class Codes: C01P 2004/84 one phase coated with the other
• CPC Class Codes: C01P 2006/42 Magnetic properties

Abstract

The invention discloses an aqueous method of making polymer coated superparamagnetic nanoparticles. Nanoparticles made by the method are included in the invention.

Claims

1. An aqueous method of making polymer coated superparamagnetic nanoparticles, the method comprising:

providing a mixture of iron salts in aqueous hydrochloric acid;

combining a solution of ammonium hydroxide with the mixture and stirring for a time sufficient for formation of a suspension of iron oxide nanoparticles;

adding to the suspension one or more aqueous biocompatible polymers thereby coating the nanoparticles with polymer, wherein optionally at least one of the polymers is aminated;

centrifuging the suspension, rendering a supernatant without large particles;

filtering the supernatant through an ultrafiltration membrane and collecting the filtrate containing the polymer coated nanoparticles;

crosslinking the polymer coating by treating the nanoparticles with epichlorohydrin and sodium hydroxide while mixing for up to about eight hours;

aminating any un-aminated crosslinked polymer remaining by treating with ammonia; and

removing free epichlorohydrin from the suspension.

2. The method of claim 1, wherein the iron salts are selected from FeCl₂, FeCl₃, and combinations thereof.

3. The method of claim 1, wherein the biocompatible polymer comprises dextran.

4. The method of claim 1, wherein the biocompatible polymer comprises silicon.

5. The method of claim 1, wherein the biocompatible polymer is selected from dextran, polyvinyl alcohol, polyacrylic acid, a silicon-based polymer and combinations thereof.

6. The method of claim 1, wherein the biocompatible polymer is selected from tetraethylorthosilicate, 3-(aminopropyl)triethoxysilane, 3-(trihydroxysylilyl)propylmethylphosphonate and combinations thereof.

7. A suspension of rod-shaped nanoparticles comprising iron oxide coated with a crosslinked aminated biocompatible polymer, said nanoparticles having a major dimension and a minor dimension, and having a relatively high magnetic R2 relaxation.

8. The suspension of claim 7, wherein said iron oxide forms a superparamagnetic core of the rod-shaped nanoparticles.

9. The suspension of claim 7, wherein said biocompatible polymer is dextran.

10. The suspension of claim 7, wherein said biocompatible polymer is selected from dextran, polyvinyl alcohol, polyacrylic acid, and combinations thereof.

11. The suspension of claim 7, wherein the minor dimension of the rod-shaped nanoparticles is approximately ⅓

of the major dimension.

12. The suspension of claim 7, wherein the major dimension of the rod-shaped nanoparticles is approximately in the range of 100-500 nm.

13. The suspension of claim 7, wherein the relatively high magnetic R2 relaxation is in the approximate range of 300-400 mMs⁻

1.

14. The suspension of claim 7, wherein the rod-shaped nanoparticles further comprise a ligand conjugated to the crosslinked aminated dextran.

15. The suspension of claim 7, wherein the rod-shaped nanoparticles further comprise a protein G ligand conjugated to the crosslinked aminated dextran.

16. A suspension of superparamagnetic nanoparticles wherein said nanoparticles comprise a core of iron oxide coated with a crosslinked aminated silicon-containing polymer, said nanoparticles having a size of approximately from 100 nm to 500 nm.

17. The suspension of superparamagnetic nanoparticles of claim 16, wherein the nanoparticles are approximately spherical and the size is a diameter.

18. The suspension of superparamagnetic nanoparticles of claim 16, wherein said nanoparticles have an R2 relaxation of approximately 150 mMs⁻

1.

19. The suspension of superparamagnetic nanoparticles of claim 16, further comprising a ligand conjugated to the crosslinked aminated silicon-containing polymer.

20. The suspension of superparamagnetic nanoparticles of claim 16, further comprising a protein G ligand conjugated to the aminated silicon-containing polymer.