Controlling the activity of growth factors, particularly TGF-β, in vivo

• US 10,092,891 B2
• Filed: 04/25/2014
• Issued: 10/09/2018
• 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.
• Primary Examiner(s): Abraham, Ibrahime A
• Assistant Examiner(s): Raphael, Colleen M
• Application Number:
  US14/261,586
• Publication Number:
  US 20150306220A1
• Time in Patent Office: 1,628 Days
• Field of Search: 530399, 530402, 204155-15821
• 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 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 nanoparticle; and

b. exposing the resulting conjugate to a radiofrequency magnetic field between approximately 100 kHz and 1 MHz, wherein the magnetic field heats the magnetic nanoparticle sufficient to release active TGF-β

from the latent TGF-β

complex.

2. The method of claim 1, wherein the radiofrequency magnetic field has a frequency from 110 kHz to 987 kHz at a field strength of 25 mT.

3. The method of claim 1, wherein the radiofrequency magnetic field has a frequency from 150 to 400 kHz at a field strength of 41 mT.

4. The method of claim 1, wherein the magnetic nanoparticle comprises iron oxide and wherein conjugating the latent TGF-β

complex to a magnetic nanoparticle comprises coating the magnetic nanoparticle with at least one of the following;

gold, polyethylene glycol, and dextran, and conjugating the latent TGF-β

complex to the coating.

5. 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 selected from microdisc or nanodisc; and

b. exposing the resulting conjugate to a low-frequency AC field having a frequency between approximately 1 Hz to 100 Hz, wherein the low-frequency AC field oscillates the microdisk or nanodisc sufficient to release active TGF-β

from the latent TGF-β

complex.

6. The method of claim 5, wherein conjugating the latent TGF-β

complex to a magnetic nanoparticle comprises coating the magnetic nanodisc or microdisc with at least one of the following;

gold, polyethylene glycol, and dextran, and conjugating the latent TGF-β

complex to the coating.

7. A method of denaturing TGF-β

, comprising;

a. providing TGF-β

conjugated to a magnetic nanoparticle; and

b. exposing the conjugate to a radiofrequency magnetic field effective to denature the TGF-β

that is conjugated to the magnetic nanoparticle.

8. The method of claim 7, wherein the magnetic nanoparticle comprises iron oxide.

9. The method of claim 7, 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,

wherein the coating conjugates the TGF-β

to the magnetic nanoparticle.