IP Library Granted Patent US 9,439,978
Granted Patent B2
US 9,439,978 · App. 14/346,330 · Granted Sep 13, 2016

Multilayered magnetic micelle compositions and methods for their use

Inventors: Subhra Mohapatra (Lutz, FL); Chunyan Wang (Tampa, FL)
Assignees: University of South Florida; The United States of America as represented by National Institutes of Health (NIH), U.S. Dept. of Health and Human Services (DHHS), U.S. Government
A61K48/0041A61K47/4823A61K47/48192A61K47/48907A61K47/48923A61K48/0033A61K49/1809A61K49/1857A61K49/1863A61K49/1875C12N15/85C12N15/88C12N2800/107C12N2810/859
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Quick Facts
Patent No.
US 9,439,978
App. No.
14/346,330
Granted
Sep 13, 2016
Kind
B2
Abstract

Provided herein are compositions comprising a micelle having a hydrophobic superparmagnetic iron oxide nanoparticle (SPION) core, a first coating comprising a cationic polymer, and a second coating comprising a polynucleotide. Also provided are methods of using the compositions for transfection and/or transformation of a cell with the polynucleotide. Further provided are methods of detecting transfection of a cell with the polynucleotide.

Claims (40)

1. A composition comprising a micelle having a hydrophobic superparamagnetic iron oxide nanoparticle (SPION) core, a first coating comprising a cationic polymer, and a second coating comprising a polynucleotide wherein the first coating comprises chitosan and polyethyleneimine (PEI), and wherein chitosan has a chemical formula of I:

wherein “m” is between 1 and 10,000; and wherein PEI has a chemical formula of II:

wherein “m” is between 1 and 10,000, and “n” is between 1 and 10,000.

2. The composition of claim 1 , wherein the micelle comprises multiple copolymers having the chemical formula of:

wherein “m” is between 1 and 10,000, “n” is between 1 and 10,000.

3. The composition of claim 2 , wherein the SPION core comprises a coating of oleic acid and oleylamine.

4. The composition of claim 3 , wherein the SPION core is prepared using iron, 1,2-dodecanediol, oleic acid, oleylamine, and benzyl ether.

5. The composition of claim 2 , wherein a molar weight ratio of chitosan and polynucleotide is between approximately 3:1 and 7:1.

6. The composition of claim 5 , wherein the polynucleotide is at a concentration between approximately 1 and 3 μg/ml.

7. The composition of claim 2 , wherein a molar weight ratio of PEI and polynucleotide is between approximately 7:1 and 3:1.

8. The composition of claim 7 , wherein the polynucleotide is at a concentration between approximately 1 and 3 μg/ml.

9. The composition of claim 2 , wherein a molar weight ratio of chitosan and PEI is between approximately 3:7 and 7:3.

10. The composition of claim 9 , wherein a molar weight ratio of chitosan and PEI is approximately 5:5.

11. The composition of claim 10 , wherein a molar weight ratio of chitosan, PEI and polynucleotide is approximately 5:5:1.

12. The composition of claim 11 , wherein the polynucleotide is at a concentration between approximately 1 and 3 μg/ml.

13. The composition of claim 1 , further comprising a ligand.

14. The composition of claim 13 , wherein in the ligand is an antibody.

15. The composition of claim 14 , wherein the antibody is specific for a prostate stem cell antigen.

16. A method of transfecting a cell with a polynucleotide comprising, contacting the cell with a composition of claim 1 .

17. The method of claim 16 , wherein the micelle comprises multiple copolymers having the chemical formula of III:

wherein “m” is between 1 and 10,000, “n” is between 1 and 10,000.

18. The method of claim 16 , further comprising placing a magnet proximal to the cell.

19. The method of claim 16 , further comprising transforming the cell.

20. The method of claim 17 , wherein a molar weight ratio of chitosan and PEI is approximately 5:5.

21. The method of claim 20 , wherein a molar weight ratio of chitosan, PEI and polynucleotide is approximately 5:5:1.

22. The method of claim 21 , wherein the polynucleotide is at a concentration between approximately 1 and 3 μg/ml.

23. The method of claim 16 , wherein the cell is in vivo.

24. The method of claim 23 , wherein the composition further comprises a cancer cell ligand and the cell is a cancer cell.

25. The method of claim 24 , wherein the cancer cell ligand is an antibody specific for prostate stem cell antigen.

26. The method of claim 16 , further comprising the step of detecting transfection of the cell using magnetic resonance imaging.

27. The method of claim 23 , further comprising the step of detecting transfection of the cell using magnetic resonance imaging.

28. A composition comprising a micelle having a hydrophobic superparamagnetic iron oxide nanoparticle (SPION) core, a first coating comprising a cationic polymer, and a second coating comprising a polynucleotide, wherein the first coating comprises polyethyleneimine and chitosan, wherein the chitosan has a chemical formula of:

wherein “m” is between 1 and 10,000;

and wherein PEI has a chemical formula of:

wherein “m” is between 1 and 10,000, and “n” is between 1 and 10,000,

wherein the micelle further comprises multiple co-polymers having the chemical formula of:

wherein “m” is between 1 and 10,000, “n” is between 1 and 10,000,

wherein the molar weight ratio of chitosan and polynucleotide is between approximately 3:1 and 7:1, the molar weight ratio of PEI and polynucleotide is between approximately 7:1 and 3:1, and the molar weight ratio of PEI to chitosan is between approximately 3:7 and 7:3.

29. The composition of claim 28 , wherein a molar weight ratio of chitosan, PEI and polynucleotide is approximately 5:5:1.

30. The composition of claim 28 , wherein the polynucleotide is at a concentration between approximately 1 and 3 μg/ml.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 22, 2014
From: MOHAPATRA, SUBHRA; WANG, CHUNYAN
To: UNIVERSITY OF SOUTH FLORIDA
Reel/Frame 034570/0403 →
CONFIRMATORY LICENSE Recorded Jun 30, 2014
From: UNIVERSITY OF SOUTH FLORIDA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 033258/0144 →
Continuity (3)
Provisional Application 61540774 · Sep 29, 2011
Provisional Application 61602391 · Feb 23, 2012
Related Publication 20150064116A1 · Mar 5, 2015