Nanoparticles for mitochondrial trafficking of agents

Patent metadata

Field	Value
Publication number	US-10416167-B2
Application number	US-201314378813-A
Country	US
Kind code	B2
Filing date	Feb 15, 2013
Priority date	Feb 17, 2012
Publication date	Sep 17, 2019
Grant date	Sep 17, 2019

Abstract

Nanoparticles include a core, a hydrophilic layer around the core, and one or more mitochondrial targeting moieties, and may optionally include one or more contrast agents or one or more therapeutic agents. For effective mitochondrial targeting the nanoparticles have a diameter of about 200 nm or less or have a zeta potential of about 0 mV or more.

First claim

What is claimed is:

1. A nanoparticle, comprising:
a hydrophobic nanoparticle core;
a hydrophilic layer surrounding the core; and
a mitochondria targeting moiety tethered to the core,
wherein the nanoparticle has a diameter of from about 10 nanometers to about 200 nanometers or less and has a zeta potential of about 0 mV or greater.

2. A nanoparticle according to claim 1 , wherein the nanoparticle has a diameter of from about 80 nanometers to about 100 nanometers.

3. A nanoparticle according to claim 1 , wherein the nanoparticle has a zeta potential of about 1 mV or greater.

4. A nanoparticle according to claim 1 , wherein the nanoparticle has a zeta potential of about 7 mV or greater.

5. A nanoparticle according to claim 1 , wherein the nanoparticle has a zeta potential of about 20 mV or greater.

6. A nanoparticle according to claim 1 , wherein the nanoparticle has a zeta potential of about 25 mV or greater.

7. A nanoparticle according to claim 1 , wherein the mitochondria targeting moiety comprises a moiety selected from the group consisting of a triphenylphosphonium (TPP) moiety, a Szeto-Shiller peptide, and a rhodamine cation.

8. A nanoparticle according to claim 1 , wherein the mitochondria targeting moiety comprises a triphenylphosphonium (TPP) moiety or a derivative thereof.

9. A nanoparticle according to claim 1 , wherein the mitochondria targeting moiety is attached to the core via a hydrophilic polymer moiety.

10. A nanoparticle according to claim 9 , wherein the hydrophilic polymer moiety comprises PEG.

11. A nanoparticle according to claim 9 , wherein the hydrophilic polymer moiety is attached to a hydrophobic polymer moiety that forms at least a portion of the core.

12. A nanoparticle according to claim 1 , wherein the hydrophilic layer comprises a hydrophilic polymer moiety attached to the core.

13. A nanoparticle according to claim 12 , wherein the hydrophilic polymer moiety comprises polyethylene glycol (PEG).

14. A nanoparticle according to claim 12 , wherein hydrophilic polymer moiety is attached to the core via a hydrophobic polymer moiety that forms at least a part of the core.

15. A nanoparticle according to claim 14 , wherein the hydrophobic polymer that forms at least a part of the core is selected from a polymer comprising polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), and polylactic-co-glycolic acid (PLGA).

16. A nanoparticle according to claim 14 , wherein the hydrophobic polymer that forms at least a part of the core comprises polylactic-co-glycolic acid (PLGA).

17. A nanoparticle according to claim 1 , further comprising a contrast agent.

18. A nanoparticle according to claim 17 , wherein the contrast agent is selected from a quantum dot, iron oxide, and combinations thereof.

19. A nanoparticle according to claim 17 , wherein the contrast agent is embedded in, or contained within, the core.

20. A nanoparticle according to claim 17 , wherein the contrast agent is attached to a hydrophilic polymer moiety that is attached to the core.

21. A nanoparticle according to claim 1 , wherein the nanoparticle further comprises a therapeutic agent.

22. A nanoparticle according to claim 21 , wherein the therapeutic agent is selected from the group consisting of an anticancer agent, a mitochondrial uncoupling agent and an agent configured to reduce amyloid beta.

23. A nanoparticle according to claim 21 , wherein the therapeutic agent is selected from the group consisting of 2,4-dinitrophenol (DNP), lonidamine (LND), α-tocopherylsuccinate (TOS), and curcumin.

24. A method for treating a patient at risk or suffering from a disease associated with mitochondrial dysfunction, comprising administering a nanoparticle according to claim 21 to the patient.

Assignees

• Univ Georgia

Inventors

• Dhar Shanta
• Marrache Sean M

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title