Preferential induction of electrically mediated cell death from applied pulses

• US 5,718,246 A
• Filed: 01/03/1996
• Issued: 02/17/1998
• Est. Priority Date: 01/03/1996
• Status: Expired due to Fees

• Current Assignee: Preferential, Inc.
• Original Assignee: Preferential, Inc.
• Inventors: Vona, Matthew J.
• Primary Examiner(s): Kamm, William E.
• Assistant Examiner(s): SCHAETZLE, KENNEDY
• Application Number:
  US08/582,509
• Time in Patent Office: 776 Days
• Field of Search: 600/10, 600/14, 607/100, 607/101, 607/102, 607/154, 607/2, 128/898
• US Class Current: 128/898
• CPC Class Codes: A61N 1/0412 Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61N 1/403 for thermotherapy, e.g. hyperthermia

Abstract

A method for inducing necrosis in susceptible malignant cells, comprises two general steps. First, positioning a collection of cells containing the susceptible malignant cells within a treatment domain, wherein the treatment domain is subjected to a non-ionizing radiation field. Second, pulsing said non-ionizing radiation field with a frequency and an intensity selected to produce necrosis in the susceptible malignant cells by creating a transmembrane potential that causes an increase in ionic diffusion in the susceptible malignant cells or generates reversible electroporation of the susceptible malignant cells. Though both malignant and non-malignant cells may be reversibly porated, it is posited that many forms of cancer will be more vulnerable to the subject procedure.

Claims

1. A method for inducing necrosis in susceptible malignant cells, comprising the steps:

a) positioning a collection of cells containing the susceptible malignant cells within a treatment domain;

b) subjecting said treatment domain to a non-ionizing radiation field;

c) pulsing said non-ionizing radiation field with a frequency and an intensity selected to produce necrosis in the susceptible malignant cells; and

d) creating by said pulsing a transmembrane potential that causes an increase in ionic diffusion in the susceptible malignant cells or generates reversible electroporation of the susceptible malignant cells.

2. A method for inducing necrosis in susceptible malignant cells, according to claim 1, wherein said pulsing frequency and intensity are selected to produce necrosis in the susceptible malignant cells based on cellular membrane characteristics of the susceptible malignant cells.

3. A method for inducing necrosis in susceptible malignant cells, according to claim 1, wherein said created transmembrane potential is about 0.2 V to about 1.5 V.

4. A method for inducing necrosis in susceptible malignant cells, according to claim 1, wherein said created transmembrane potential is about 0.2 V to about 0.7 V.

5. A method for inducing necrosis in susceptible malignant cells, according to claim 1, wherein said induced necrosis in the susceptible malignant cells is caused by said increase in ionic diffusion.

6. A method for inducing necrosis in susceptible malignant cells, according to claim 1, wherein the induced necrosis in the susceptible malignant cells is generated by said reversible electropotation.

7. A method for inducing necrosis in susceptible malignant cells, according to claim 1, further comprising the step of causing, from said created transmembrane potential, an oscillation in calcium, sodium, or potassium ion concentration in the susceptible malignant cells, thereby causing a lethal metabolic alteration in the susceptible malignant cells.

8. A method for inducing necrosis in susceptible malignant cells, according to claim 1, further comprising the step of causing, from said created transmembrane potential, an increase in ATP usage in the susceptible malignant cells, thereby causing a lethal metabolic alteration in the susceptible malignant cells.

9. A method for inducing necrosis in susceptible malignant cells, according to claim 1, further comprising the step of causing, from said created transmembrane potential, a deleterious internal pH in the susceptible malignant cells, thereby causing a lethal metabolic alteration in the susceptible malignant cells.

10. A method for inducing necrosis in susceptible malignant cells, comprising the steps:

a) positioning a collection of cells containing the susceptible malignant cells within a treatment domain;

b) subjecting said treatment domain to a non-ionizing radiation field;

c) pulsing said non-ionizing radiation field with pulses having a pulse duration, interval gap between pulses, and pulse intensity selected to produce necrosis in the susceptible malignant cells; and

d) creating by said pulsing a transmembrane potential that causes an increase in ionic diffusion in the susceptible malignant cells or generates reversible electroporation of the susceptible malignant cells, thereby causing a lethal metabolic alteration in the susceptible malignant cells.

11. A method for inducing necrosis in susceptible malignant cells, according to claim 10, wherein said pulse duration, interval gap between pulses, and pulse intensity are selected to produce necrosis in the susceptible malignant cells based on cellular membrane characteristics of the susceptible malignant cells.

12. A method for inducing necrosis in susceptible malignant cells, according to claim 10, wherein said created transmembrane potential is about 0.2 V to about 1.5 V.

13. A method for inducing necrosis in susceptible malignant cells, according to claim 10, wherein said created transmembrane potential is about 0.2 V to about 0.7 V.

14. A method for inducing necrosis in susceptible malignant cells, according to claim 10, wherein said lethal metabolic alteration in the susceptible malignant cells is caused by said increase in ionic diffusion.

15. A method for inducing necrosis in susceptible malignant cells, according to claim 10, wherein said lethal metabolic alteration in the susceptible malignant cells is generated by said reversible electroporation.

16. A method for inducing necrosis in susceptible malignant cells, according to claim 10, further comprising the step of causing, from said created transmembrane potential, an oscillation in calcium, sodium, or potassium ion concentration in the susceptible malignant cells, thereby causing a lethal metabolic alteration in the susceptible malignant cells.

17. A method for inducing necrosis in susceptible malignant cells, according to claim 10, further comprising the step of causing, from said created transmembrane potential, an increase in ATP usage in the susceptible malignant cells, thereby causing a lethal metabolic alteration in the susceptible malignant cells.

18. A method for inducing necrosis in susceptible malignant cells, according to claim 10, further comprising the step of causing, from said created transmembrane potential, a deleterious alteration in internal pH in the susceptible malignant cells, thereby causing a lethal metabolic alteration in the susceptible malignant cells.

19. A method for treating a patient having malignant cells, wherein the treatment induces necrosis in the malignant cells that are susceptible to said treatment, comprising the steps:

a) selecting the patient with the malignant cells that are susceptible to the treatment because the susceptible malignant cells produce ATP primarily through glycolytic pathways or the susceptible malignant cells have a variant ion gradient relative to nonsusceptible healthy cells;

b) positioning the patient to place the susceptible malignant cells within a treatment domain;

c) subjecting said treatment domain to a non-ionizing radiation field; and

d) pulsing said non-ionizing radiation field with pulses having a pulse duration, interval gap between pulses, and pulse intensity selected to produce necrosis in the susceptible malignant cells by creating a transmembrane potential that causes an increase in ionic diffusion in the susceptible malignant cells or generates reversible electroporation of the susceptible malignant cells, thereby causing a lethal metabolic alteration in the susceptible malignant cells.

20. A method for inducing necrosis in susceptible malignant cells, according to claim 19, wherein said created transmembrane potential is about 0.2 V to about 1.5 V.

21. A method for inducing necrosis in susceptible malignant cells, according to claim 19, wherein said created transmembrane potential is about 0.2 V to about 0.7 V.

22. A method for inducing necrosis in susceptible malignant cells, according to claim 19, wherein said lethal metabolic alteration in the susceptible malignant cells is caused by said increase in ionic diffusion.

23. A method for inducing necrosis in susceptible malignant cells, according to claim 19, wherein said lethal metabolic alteration in the susceptible malignant cells is generated by said reversible electropotation.

24. A method for inducing necrosis in susceptible malignant cells, according to claim 19, further comprising the step of causing, from said created transmembrane potential, an oscillation in calcium, sodium, or potassium ion concentration in the susceptible malignant cells, thereby causing a lethal metabolic alteration in the susceptible malignant cells.

25. A method for inducing necrosis in susceptible malignant cells, according to claim 19, further comprising the step of causing, from said created transmembrane potential, an increase in ATP usage in the susceptible malignant cells, thereby causing a lethal metabolic alteration in the susceptible malignant cells.

26. A method for inducing necrosis in susceptible malignant cells, according to claim 19, further comprising the step of causing, from said created transmembrane potential, a deleterious alteration in internal pH in the susceptible malignant cells, thereby causing a lethal metabolic alteration in the susceptible malignant cells.