IP Library Granted Patent US 8,916,134
Granted Patent B2
US 8,916,134 · App. 12/171,812 · Granted Dec 23, 2014

Metal nanocomposite, preparation method and use thereof

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Quick Facts
Patent No.
US 8,916,134
App. No.
12/171,812
Granted
Dec 23, 2014
Kind
B2
Abstract

The disclosure provides metal nanocomposites including one or more metal nanoparticles having a hydrophobic surface and at least partially enclosed by cationic and hydrophilic polymers. The metal nanocomposites are useful as among others, a contrast agent, a diagnostic composition or a pharmaceutical composition.

Claims (46)

1. A metal nanocomposite comprising one or more metal nanoparticles having a hydrophobic surface; and one or more cationic and hydrophilic polymers associated with the hydrophobic surface;

wherein:

the one or more metal nanoparticles is MnFe 2 O 4 ;

the hydrophobic surface contains an organic surfactant having one or more hydrophobic moieties; and

the one or more cationic and hydrophilic polymers are selected from the group consisting of: polyethyleneimine, polyacrylamide, and polyornithine.

2. The metal nanocomposite of claim 1 , wherein the one or more cationic and hydrophilic polymers enclose at least partially the hydrophobic surface.

3. The metal nanocomposite of claim 1 , wherein the one or more metal nanoparticles have an average diameter of about 1 nm to about 1,000 nm.

4. The metal nanocomposite of claim 1 , wherein the one or more cationic and hydrophilic polymers form a shell that has an average thickness of about 1 nm to about 40 nm.

5. The metal nanocomposite of claim 1 , wherein the at least one organic surfactant is selected from the group consisting of: an alkyl trimethylammonium halide; a saturated fatty acid; an unsaturated fatty acid; a trialkylphosphine; a trialkylphosphine oxide; an alkylamine; an alkyl thiol; a sodium alkyl sulfate; and a sodium alkylphosphate.

6. The metal nanocomposite of claim 5 , wherein the at least one organic surfactant is selected from the group consisting of: oleic acid; lauric acid; dodecylic acid; and dodecyl amine.

7. The metal nanocomposite of claim 1 , wherein the one or more cationic and hydrophilic polymers have an average molecular weight (Mw) of about 1,000 to about 1,000,000.

8. The metal nanocomposite of claim 7 , wherein the one or more cationic and hydrophilic polymers have a weight average molecular weight (Mw) of about 2,000 to about 30,000.

9. The metal nanocomposite of claim 1 , wherein the one or more cationic and hydrophilic polymers are bound to an active substance selected from the group consisting of: a cell; an antigen; an antibody; a nucleic acid; a polypeptide; an organic fluorescent material; a carbohydrate; a lipid; a tumor marker-specific binding material; and a pharmaceutically active ingredient.

10. The metal nanocomposite of claim 9 , wherein the active substance is bound to one or more amine groups of the one or more cationic and hydrophilic polymers.

11. The metal nanocomposite of claim 9 , wherein the nucleic acid comprises DNA or RNA.

12. The metal nanocomposite of claim 9 , wherein the organic fluorescent material comprises RITC (rhodamin A isothiocyanate) or FITC (fluorescein isothiocyanate).

13. The metal nanocomposite of claim 9 , wherein the tumor marker-specific binding material comprises one or more materials selected from the group consisting of: phosphatidylserine; VEGFR; an integrin receptor; a Tie2 receptor; a somatostatin receptor; a vasointestinal peptide receptor; Herceptin; Rituxan; and folic acid.

14. The metal nanocomposite of claim 9 , wherein the pharmaceutically active ingredient comprises one or more agents selected from the group consisting of: an anticancer agent; an antibiotic; a hormone; a hormone antagonist; an interleukin; an interferon; a growth factor; a tumor necrosis factor; an endotoxin; a lymphotoxin; a eurokinase; a streptokinase; a tissue plasminogen activator; a protease inhibitor; an alkylphosphocholine; a radioisotope labeled component; a surfactant; a cardiovascular system drug; a gastrointestinal system drug; and a nervous system drug.

15. The metal nanocomposite of claim 1 , whrein the one or more cationic and hydrophilic polymers is polyethyleneimine.

16. A contrast composition comprising the metal nanocomposite of claim 1 and a pharmaceutically acceptable carrier or excipient.

17. A diagnosis composition comprising the metal nanocomposite of claim 1 and a pharmaceutically acceptable carrier or excipient.

18. The diagnosis composition of claim 17 , wherein the one or more cationic and hydrophilic polymers in the metal nanocomposite are bound to an active substance selected from the group consisting of: a cell; an antigen; an antibody; a nucleic acid; a polypeptide; an organic fluorescent material; a carbohydrate; a lipid; a tumor marker-specific binding material; and a pharmaceutically active ingredient.

19. A pharmaceutical composition comprising the metal nanocomposite of claim 1 and a pharmaceutically acceptable carrier.

20. A method for preparing a metal nanocomposite of claim 1 comprising:

providing an aqueous solution containing one or more cationic and hydrophilic polymers to an organic solution containing one or more metal nanoparticles having hydrophobic surface, to form an emulsion; and

removing the organic solvent from the emulsion to form a metal nanocomposite preparation;

wherein:

the one or more metal nanoparticles is MnFe 2 O 4 ;

the hydrophobic surface contains an organic surfactant having one or more hydrophobic moieties; and

the one or more cationic and hydrophilic polymers are selected from the group consisting of: polyethyleneimine, polyarcylamide, and polyornithine.

21. The method of claim 20 , wherein the method further comprises binding the cationic and hydrophilic polymer with an active substance selected from the group consisting of: a cell; an antigen; an antibody; a nucleic acid; a polypeptide; an organic fluorescent material; a carbohydrate; a lipid; a tumor marker-specific binding material; and a pharmaceutically active ingredient.

22. The method of claim 20 , wherein the method further comprises performing a thermal decomposition reaction of a hydrophobic surface stabilizer and a precursor of the metal nanoparticle in a solvent to form the one or more metal nanoparticles having a hydrophobic surface.

23. The method of claim 22 , wherein the precursor comprises a metal carbonyl compound or a metal acetylacetonate compound.

24. The method of claim 20 , wherein the organic solution comprises one or more solvents selected from the group consisting of: hexane; chloroform; benzene; diethylether; ethyl acetate; and dichloromethane.

25. The method of claim 20 , wherein the aqueous solution comprises one or more solvents selected from the group consisting of: water; PBS; alcohol; and dimethylsulfoxide.

26. The method of claim 20 , wherein the emulsion is formed under ultrasonication.

27. The method of claim 20 , wherein the organic solvent is removed by evaporation.

28. A method for using a contrast composition to image the cells or tissues of a subject, the method comprising:

(a) administering an effective amount of a contrast composition comprising the metal nanocomposite of claim 1 and a pharmaceutically acceptable carrier or excipient to a subject; and

(b) detecting a signal emitted by the metal nanocomposite from the subject to obtain images of the cells or tissues of the subject.

29. A method for diagnosing a medical condition, the method comprising:

(a) administering an effective amount of a diagnosis composition comprising the metal nanocomposite of claim 1 and a pharmaceutically acceptable carrier or excipient to a subject; and

(b) detecting a signal emitted by the metal nanocomposite from the subject to obtain images, wherein the image is compared to a reference standard in order to diagnose the medical condition in the subject.

30. A method for simultaneously diagnosing and treating a medical condition, the method comprising:

(a) administering a therapeutically effective amount of a pharmaceutical composition comprising the metal nanocomposite of claim 1 and a pharmaceutically acceptable carrier or excipient to a subject, wherein the pharmaceutical composition is bound to an active substance; and

(b) detecting a signal emitted by the metal nanocomposite from the subject to obtain an image, wherein the image is compared to a reference standard in order to diagnose the medical condition in the subject and the active substance treats the medical condition in the subject.

Assignments (4)
RELEASE OF SECURITY INTEREST IN PATENTS, RECORDED ON JANUARY 29, 2019 AT REEL 048373 FRAME 0217 Recorded Sep 22, 2025
From: CRESTLINE DIRECT FINANCE, L.P., AS COLLATERAL AGENT
To: EMPIRE TECHNOLOGY DEVELOPMENT LLC
Reel/Frame 072936/0464 →
RELEASE OF SECURITY INTEREST Recorded Jul 31, 2019
From: CRESTLINE DIRECT FINANCE, L.P.
To: EMPIRE TECHNOLOGY DEVELOPMENT LLC
Reel/Frame 049924/0794 →
SECURITY INTEREST Recorded Jan 29, 2019
From: EMPIRE TECHNOLOGY DEVELOPMENT LLC
To: CRESTLINE DIRECT FINANCE, L.P.
Reel/Frame 048373/0217 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 22, 2010
From: HAAM, SEUNG JOO; SEO, SUNG BAEK; YANG, JAE MOON
To: INDUSTRY-ACADEMIC COOPERATION FOUNDATION, YONSEI UNIVERSITY
Reel/Frame 023969/0045 →