Magnetic nanoparticle composition and manufacturing method and use thereof

Patent metadata

Field	Value
Publication number	US-9775824-B2
Application number	US-201414295442-A
Country	US
Kind code	B2
Filing date	Jun 4, 2014
Priority date	Jun 4, 2014
Publication date	Oct 3, 2017
Grant date	Oct 3, 2017

Abstract

The present invention provides a magnetic nanoparticle composition, comprising an iron oxide particle core conjugated with a capping agent and having wüstite structure and antiferromagnetic properties, wherein the empirical formula of iron oxide is defined as Fe x O with x in the range of about 0.83 to about 0.96. Also provided are a method of manufacturing the same, a contrast agent comprising the same, and methods of using the same for acquiring a magnetic resonance image and for delivering a therapeutic or diagnostic agent.

First claim

What is claimed is:

1. A magnetic nanoparticle composition, comprising an iron oxide particle core conjugated with a capping agent and having wüstite structure and antiferromagnetic properties, wherein the empirical formula of iron oxide is defined as Fe x O with x in the range of about 0.83 to about 0.96, and wherein the iron oxide particle core exhibits an r 2 /r 1 ratio of about 1 to about 10, where r 2 represents transverse relaxivity and r 1 represents longitudinal relaxivity.

2. The composition according to claim 1 , which is in an aqueous phase and has a pH of about 4 to about 12.

3. The composition according to claim 1 , wherein the iron oxide particle core has a particle size of less than 50 nm.

4. The composition according to claim 3 , wherein the iron oxide particle core has a particle size of less than 20 nm.

5. The composition according tea claim 1 , wherein the capping agent is a biocompatible capping agent selected from a group consisting of glutathione, glutamic acid, dextrin, starch, glucose, chitosan, citrate, citric acid, ascorbic acid, insulin, bovine serum albumin, keratin, arginine, curcumin and protamine.

6. The composition according to claim 5 , wherein the biocompatible capping agent is glutathione.

7. The composition according to claim 5 , wherein the capping agent is conjugated with a targeting agent or a therapeutic agent.

8. A method of manufacturing the composition according to claim 1 , comprising:
preparing a mixture containing ferrous salt, ferric salt and the capping agent; and
adding a reducing agent to the mixture to initiate a redox reaction at room temperature, thereby forming the iron oxide particle core conjugated with the capping agent;
wherein the composition is in an aqueous phase.

9. The method according to claim 8 , wherein the molar ratio of [Fe 2+ ] to [Fe 3+ ] is about 0.2 to about 5.

10. The method according to claim 9 , wherein the molar ratio of [Fe 2+ ] to [Fe 3+ ] is about 0.5 to about 2.

11. The method according to claim 8 , wherein the reducing agent is selected from a group consisting of tetrakis(hydroxymethyl)phosphonium chloride, borohydride, hydrazine, caustic alkali, hydroxyl amine, ammonium hydroxide, citrate, citric acid, ascorbic acid and a mixture thereof.

12. The method according to claim 11 , wherein the reducing agent is tetrakis(hydroxymethyl) phosphonium chloride.

13. The method according to claim 8 , wherein the ferrous salt is selected from a group consisting of ferrous chloride, ferrous chloride tetrahydrate, ferrous acetate, ferrous lactate, ferrous: oxalate and a mixture thereof; and the ferric salt is selected from a group consisting of ferric chloride, ferric chloride hexahydrate, ferric acetate, ferric acetylacetonate, ferric oxalate, ferric nitrate, ferric nitrate nonahydrate and a mixture thereof.

14. The method according to claim 8 , wherein the capping agent is a biocompatible capping agent selected from a group consisting of glutathione, glutamic acid, dextrin, starch, glucose, chitosan, citrate, citric acid, ascorbic acid, fatty acid, insulin, bovine serum albumin, keratin, arginine, curcumin and protamine.

15. The method according to claim 14 , wherein the biocompatible capping agent is glutathione.

16. A contrast agent for magnetic resonance imaging comprising the composition according to claim 1 .

17. The contrast agent of claim 16 , which is a T 1 contrast agent.

18. A method of acquiring an image, comprising:
administering the contrast agent according to claim 16 to a recipient; and
acquiring a magnetic resonance image of the recipient.

19. A method for delivering a therapeutic or diagnostic agent, comprising administering the composition according to claim 1 to a recipient, wherein the therapeutic or diagnostic agent is conjugated with the iron oxide particle core or the capping agent.

Assignees

• Univ Nat Taiwan

Inventors

• Chou Pi-Tai
• Liu Chien-Liang

Classifications

• Y10T428/2982

  Particulate matter [e.g., sphere, flake, etc.] · CPC title

• A61K31/295 Primary

  Iron group metal compounds · CPC title

• A61K49/1866

  the nanoparticle having a (super)(para)magnetic core coated or functionalised with a peptide, e.g. protein, polyamino acid · CPC title