Controlling the activity of growth factors, particularly tgf-beta, in vivo

Patent metadata

Field	Value
Publication number	US-2015306220-A1
Application number	US-201414261586-A
Country	US
Kind code	A1
Filing date	Apr 25, 2014
Priority date	Apr 25, 2014
Publication date	Oct 29, 2015
Grant date	—

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.

First claim

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.

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.

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.

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.

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.

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.

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.

Assignees

• Univ Florida

Inventors

• Monsalve Adam
• Dobson Jon P

Classifications

• A61K38/1841 Primary

  Transforming growth factor [TGF] · CPC title

• A61K9/0009

  involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis · CPC title

• A61K47/6923

  the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb · CPC title

• B01J19/087 Primary

  employing electric or magnetic energy · CPC title

• A61K47/48015

  Human Necessities · mapped topic