Multilayered magnetic micelle compositions and methods for their use

Patent metadata

Field	Value
Publication number	US-9439978-B2
Application number	US-201214346330-A
Country	US
Kind code	B2
Filing date	Sep 28, 2012
Priority date	Sep 29, 2011
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

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.

First claim

The invention claimed is:

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.

Assignees

• Mohapatra Subhra
• Wang Chunyan
• Univ South Florida
• The United States Of America As Represented By Nat Inst Of Health (Nih) U S Dept Of Health And Human

Inventors

• Mohapatra Subhra
• Wang Chunyan

Classifications

• C12N2800/107

  for mammalian · CPC title

• A61K49/1857

  the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA · CPC title

• A61K49/1875

  coated or functionalised with an antibody · CPC title

• A61K47/48192

  Human Necessities · mapped topic

• C12N2810/859

  from immunoglobulins · CPC title