IRREVERSIBLE ELECTROPORATION USING NANOPARTICLES

• US 20100331758A1
• Filed: 10/30/2009
• Published: 12/30/2010
• Est. Priority Date: 04/29/2008
• Status: Active Grant

• Current Assignee: Christopher B. Arena, Marissa N. Rylander, Rafael V. Davalos
• Original Assignee: Virginia Tech Intellectual Properties, Inc.
• Inventors: ARENA, Christopher B., RYLANDER, Marissa N., DAVALOS, Rafael V.
• Granted Patent: US 8,465,484 B2
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61B 18/1206 Generators therefor
• CPC Class Codes: A61B 18/1477 Needle-like probes
• CPC Class Codes: A61B 2018/00446 Brain
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation reversible electroporation A61N1/327
• CPC Class Codes: A61N 1/05 for implantation or insertion into the body, e.g. heart electrode A61N1/06 takes precedence
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves

Abstract

The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. The invention can be used to treat solid tumors, such as brain tumors. The methods rely on non-thermal irreversible electroporation (IRE) to cause cell death in treated tumors. In embodiments, the methods comprise the use of high aspect ratio nanoparticles with or without modified surface chemistry.

Claims

1. A method of treating a subject suffering from a neoplasia, said method comprising:

administering nanoparticles to the subject in an amount sufficient to permit at least some of the nanoparticles to come in close proximity to neoplastic cells;

implanting at least one device suitable for use in Irreversible Electroporation (IRE) into or adjacent the neoplastic cells within the body of the subject;

causing multiple electrical pulses to be emitted from the electrically conductive region(s) into the neoplasia at about 500 V/cm to about 1500 V/cm in 90 microsecond or less pulses to cause predominantly non-thermal killing of neoplastic cells; and

removing the device(s) from the body of the subject.

2. The method of claim 1, wherein the neoplasia is leukemia.

3. The method of claim 2, wherein the neoplastic cells are present in the bone marrow of the subject.

4. The method of claim 1, wherein the neoplasia is a solid tumor.

5. The method of claim 4, wherein the method results in a reduction in tumor size.

6. The method of claim 1, wherein the subject is a human.

7. The method of claim 1, wherein the electrical pulses are each 50 microseconds or less.

8. The method of claim 1, wherein two or more devices are used.

9. The method of claim 1, wherein the method results in a reduction in cell proliferation of cells of the neoplasia.

10. The method of claim 1, wherein the method results in ablation of a sufficient number of neoplastic cells to result in long-term survival of the subject from the neoplasia.

11. The method of claim 1, wherein causing multiple electrical pulses to be emitted comprises limiting the total charge delivered to the subject to minimize disruption of or damage to healthy tissue surrounding the neoplastic cells.

12. The method of claim 1, wherein the method comprises administering 90 pulses or more.

13. The method of claim 1, wherein the current is monitored in real-time and, based on that monitoring, excessive charge delivery is mitigated to reduce damage to healthy tissue.

14. The method of claim 1, wherein the current is monitored in real-time and, based on that monitoring, thermal energy dose is not excessive, reducing damage to healthy tissue.

15. A method of treating a subject suffering from a neoplasia, said method comprising:

implanting at least one device suitable for use in Irreversible Electroporation (IRE) into or adjacent a neoplastic site within the body of a subject;

introducing nanoparticles into or adjacent the neoplastic site;

causing multiple electrical pulses to be emitted from electrically conductive region(s) of the device into the tumor at about 500 V/cm to about 1500 V/cm in 90 microsecond or less pulses to cause predominantly non-thermal killing of neoplastic cells; and

removing the device(s) from the body of the subject.

16. The method of claim 15, wherein the neoplasia is leukemia.

17. The method of claim 15, wherein the neoplasia is a brain tumor.

18. The method of claim 15, wherein the subject is a human.

19. The method of claim 15, wherein the electrical pulses are each 50 microseconds or less.

20. The method of claim 15, wherein the nanoparticles comprise fullerenes, endohedral metallofullerenes, trimetallic nitride templated endohedral metallofullerenes, single-walled and multi-walled carbon nanotubes, gold nanorods, silver nanorods, single-walled and multi-walled boron/nitrade nanotubes, carbon nanotube peapods, carbon nanohorns, carbon nanohorn peapods, liposomes, nanoshells, dendrimers, quantum dots, superparamagnetic nanoparticles, nanorods, polystyrene beads, glass and polymer micro- and nano-spheres, biodegradable micro- and nano-spheres, cellulose nanocrystals, gold, silver, carbon, and iron nanoparticles, or a combination of two or more of these.

21. The method of claim 15, wherein the target concentration of nanoparticle solutions range from 0.1 ug/ml to 100 mg/ml.

22. The method of claim 15, wherein cells beyond the IRE zone of ablation are electroporated.

23. The method of claim 15, wherein the cells beyond the IRE zone of ablation are reversibly electroporated.

24. The method of claim 15, wherein the nanoparticles are introduced in an amount sufficient to increase the IRE zone of ablation beyond the zone achievable in the absence of the nanoparticles.