CONTROLLING THE ACTIVITY OF GROWTH FACTORS, PARTICULARLY TGF-BETA, IN VIVO

• US 20150306220A1
• Filed: 04/25/2014
• Published: 10/29/2015
• Est. Priority Date: 04/25/2014
• Status: Active Grant

• Current Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Original Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Inventors: Monsalve, Adam, Dobson, Jon P.
• Granted Patent: US 10,092,891 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61K 47/6923 the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: B01J 19/087 employing electric or magnetic energy

Abstract

TGF-β growth factor and its latent complex are conjugated to magnetic micro- or nanoparticles and to magnetic micro- or nanodiscs. By exposing the resulting conjugates to magnetic fields, the TGF-β growth factor can be released from its latent complex in vivo, potentially making it useful in tissue engineering and regenerative medicine. And by exposing a conjugate of TGF-β growth factor and a magnetic particle to a sufficiently strong, radiofrequency magnetic field, the TGF-β growth factor can be denatured and thereby deactivated, potentially making it possible to avoid triggering tumorigenesis, atherosclerosis, fibrotic disease, and cancer.

Claims

1. A conjugate of TGF-β

and a magnetizable particle.

2. The conjugate of claim 1, wherein the magnetic particle is surface-functionalized.

3. The conjugate of claim 2, wherein the magnetic particle is iron oxide and coated with polyethylene glycol.

7. The conjugate of claim 1, 2, 3, 4, 5, or 6, wherein the magnetic particle is a nano- or microparticle.

8. The conjugate of claim 1, 2, 3, 4, 5, or 6, wherein the magnetic particle is a nano- or microdisc.

4. A conjugate of latent TGF-β

complex and a magnetic particle.

5. The conjugate of claim 4, wherein the magnetic particle is surface-functionalized.

6. The conjugate of claim 5, wherein the magnetic particle is iron oxide and coated with polyethylene glycol.

9. A conjugate of a magnetic iron oxide particle that is coated with polyethylene glycol and either

a. a growth factor;

or

b. a latent growth factor complex.

10. The conjugate of claim 9, wherein the growth factor is TGF-β

and the latent growth factor is TGF-β

complex.

12. The conjugates of claim 9, 10, or 11, wherein the particle is a nanoparticle.

13. The conjugates of claim 9, 10, or 11, wherein the particle is a nanodisc.

11. A conjugate of a magnetic iron oxide particle that is coated with polyethylene glycol and either:

a. a cytokine;

or

b. a latent cytokine complex.

14. A conjugate of TGF-β

and a magnetic nanoparticle having a coating selected from the following;

a. gold;

b. dextran;

c. polyethylene glycol;

or

d. a biocompatible polymer.

15. A conjugate of latent TGF-β

complex and a magnetic nanoparticle having a coating selected from the following;

a. gold;

b. dextran;

c. polyethylene glycol;

or

d. a biocompatible polymer.

16. A conjugate of latent TGF-β

complex and a magnetic spin vortex permalloy micro- or nanodisc, the micro- or nanodisk having gold-coated top and bottom surfaces and an uncoated peripheral edge.

17. A method of releasing active TGF-β

from a latent TGF-β

complex in which it is sequestered, comprising;

a. conjugating the latent TGF-β

complex to a magnetic particle; and

b. exposing the resulting conjugate to a magnetic field.

18. The method of claim 17, wherein the particle is a nanoparticle.

19. The method of claim 18, wherein the magnetic field is a radiofrequency magnetic field.

20. The method of claim 19, wherein the magnetic field has a frequency between approximately 100 kHz and 1 MHz.

21. The method of claim 17, wherein the particle is a micro- or nanodisc.

22. The method of claim 21, wherein the magnetic field is a low-frequency AC field.

23. The method of claim 22, wherein the magnetic field has a frequency between approximately 1 Hz to 100 Hz.

24. A method of denaturing TGF-β

, comprising;

a. conjugating the TGF-β

to a magnetic nanoparticle; and

b. exposing the conjugate to a magnetic field.

25. The method of claim 24, wherein the magnetic field is a radiofrequency magnetic field.

26. The method of claim 24, wherein the magnetic nanoparticle is of iron oxide coated with at least one of the following:

a. gold;

b. polyethylene glycol;

c. dextran; and

d. a biocompatible polymer.

27. A conjugate of a growth factor and a magnetic particle.