COMPOSITION AND METHOD FOR CANCER TREATMENT USING TARGETED SINGLE-WALLED CARBON NANOTUBES

• US 20080227687A1
• Filed: 02/19/2008
• Published: 09/18/2008
• Est. Priority Date: 02/19/2007
• Status: Abandoned Application

• Current Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: Resasco, Daniel E., Harrison, Roger G.
• Application Number:
  US12/033,857
• Publication Number:
  US 20080227687A1
• Time in Patent Office: Days
• US Class Current: 514/2
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61N 2005/0659 infrared
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention is a method for detecting and destroying cancer tumors. The method is based on the concept of associating a linking protein or linking peptide such as, but not limited to, annexin V or other annexins to single-walled carbon nanotubes (SWNT) to form a protein-SWNT complex. Said linking protein or peptide can selectively bind to cancerous cells, especially tumor vasculature endothelial cells, rather than to healthy ones by binding to cancer-specific external receptors such as anionic phospholipids including phosphatidylserine expressed on the outer surfaces of cancer cells only. Irradiation of bound SWNTs with specific wavelength is then used to detect and destroy those cells to which the SWNTs are bound via the linking protein or peptide thereby destroying the tumor or cancer cells.

Claims

1. A method of treating a cancer tumor or cancer cells in a patient, comprising:

providing a composition comprising a protein-carbon nanotube complex comprising a protein or peptide operatively attached to a carbon nanotube, wherein the protein or peptide of the protein-carbon nanotube complex comprises a binding protein or peptide that has binding specific for an external receptor or binding site on a tumor vasculature endothelial cell or on a cancer cell;

administering the composition comprising the protein-carbon nanotube complex to the patient wherein the protein-carbon nanotube complex preferentially binds via the binding protein or peptide to the external receptor or binding site on an outer surface of the endothelial cell of the tumor vasculature of the cancer tumor or on an outer surface of the cancer cell in the patient; and

exposing the patient to electromagnetic radiation comprising a wavelength absorbable by the carbon nanotube causing elevation of the temperature of the carbon nanotube of the protein-carbon nanotube complex to a temperature which induces damage or death of the endothelial cell of the tumor vasculature or of the cancer cell to which the protein-carbon nanotube complex is bound.

2. The method of claim 1 wherein the external receptor or binding site is specific for the tumor vasculature endothelial cells or cancer cells

3. The method of claim 1 wherein the carbon nanotube of the protein-carbon nanotube complex is a single-walled carbon nanotube.

4. The method of claim 3 wherein the single-walled carbon nanotube has a (6,5) or (7,6) structure.

5. The method of claim 1 wherein the composition comprises a plurality of protein-carbon nanotube complexes having a plurality of absorbable wavelengths.

6. The method of claim 5 wherein the composition comprises at least 25% of a single protein-carbon nanotube complex.

7. The method of claim 3 wherein the composition comprises at least 25% of a single type of (n,m) structure.

8. The method of claim 1 wherein the external receptor or binding site is at least one of phosphatidylserine, phosphatidylinositol, phosphatidic acid, or phosphatidylglycerol.

9. The method of claim 1 wherein the binding protein or peptide is attached to the carbon nanotube via a cellulose derivative.

10. The method of claim 9 wherein the cellulose derivative is carboxymethylcellulose, hydroxymethylcellulose, or hydroxypropylcellulose.

11. The method of claim 1 wherein the absorbable wavelength is a near-infrared wavelength.

12. The method of claim 1 wherein the absorbable wavelength is 980 nm±

50 nm or 1120 nm±

50 nm.

13. The method of claim 3 wherein the single-walled carbon nanotube of the protein-carbon nanotube complex has an S11 transition of at least 50% of background.

14. The method of claim 1 wherein the protein of the protein-carbon nanotube complex is an annexin.

15. A method of treating a cancer tumor or cancer cells in a patient, comprising:

providing a protein-carbon nanotube complex comprising a carbon nanotube having bound thereto a protein or peptide which binds with high specificity to at least one of phosphatidylserine, phosphatidylinositol, phosphatidic acid, or phosphatidylglycerol;

administering the protein-carbon nanotube complex to the patient wherein the protein-carbon nanotube complex preferentially binds to phosphatidylserine, phosphatidylinositol, phosphatidic acid, or phosphatidylglycerol expressed on an outer surface of an endothelial cell of a vasculature of the cancer tumor or on an outer surface of the cancer cell in the patient; and

exposing the patient to electromagnetic radiation comprising a wavelength absorbable by the carbon nanotube of the protein-carbon nanotube complex causing elevation of the temperature of the carbon nanotube of the protein-carbon nanotube complex to a temperature which induces damage or death of the endothelial cell of the tumor vasculature or of the cancer cell to which the protein-carbon nanotube complex is bound.

16. The method of claim 15 wherein the protein of the protein-carbon nanotube complex is an annexin.

17. The method of claim 15 wherein the binding protein or peptide is attached to the carbon nanotube via a cellulose derivative.

18. The method of claim 17 wherein the cellulose derivative is carboxymethylcellulose, hydroxymethylcellulose, or hydroxypropylcellulose.

19. The method of claim 15 wherein the carbon nanotube of the protein-carbon nanotube complex is a single-walled carbon nanotube.

20. The method of claim 19 wherein the single-walled carbon nanotube has a (6,5) or (7,6) structure.

21. The method of claim 19 wherein the composition comprises at least 25% of a single type of (n,m) structure.

22. The method of claim 15 wherein the composition comprises a plurality of protein-carbon nanotube complexes having a plurality of absorbable wavelengths.

23. The method of claim 22 wherein the composition comprises at least 25% of a single protein-carbon nanotube complex.

24. The method of claim 19 wherein the single-walled carbon nanotube of the protein-carbon nanotube complex has an S11 transition of at least 50% of background.

25. The method of claim 19 wherein the absorbable wavelength to which the patient is exposed is a near-infrared wavelength.

26. The method of claim 19 wherein the absorbable wavelength is 980 nm±

50 nm or 1120 nm±

50 nm.

27. A protein-carbon nanotube complex for binding to phosphatidylserine, phosphatidylglycerol, phosphatidic acid, or phosphatidylethanolamine on a cancer cell or tumor vasculature endothelial cell in vivo, comprising:

a single-walled carbon nanotube and a binding protein or peptide operatively attached to the single-walled carbon nanotube to form the protein-SWNT complex, wherein the binding protein or peptide is specific for phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, or phosphatidic acid.

28. The protein-carbon nanotube complex of claim 27 primarily comprising single walled carbon nanotubes having a (6,5) or (7,6) structure.

29. The protein-carbon nanotube complex of claim 27 further comprising a polyalkylene glycol adsorbed to the single-walled carbon nanotube, wherein the binding protein or peptide is operatively associated with the single-walled carbon nanotube via the polyalkyleneglycol.

30. The protein-carbon nanotube complex of claim 27 wherein the binding protein or peptide is attached to the single-walled carbon nanotube via a cellulose derivative which is adsorbed upon the single-walled carbon nanotube.

31. The protein-carbon nanotube complex of claim 30 wherein the cellulose derivative is carboxymethylcellulose, hydroxymethylcellulose or hydroxypropylcellulose.

32. The protein-carbon nanotube complex of claim 27 wherein the binding protein is an annexin.

33. The protein-carbon nanotube complex of claim 27 wherein the single-walled carbon nanotube has an absorption wavelength in the near-infrared range.

34. The protein-carbon nanotube complex of claim 27 wherein the single-walled carbon nanotube has an absorption wavelength of 980 nm±

50 nm or 1120 nm±

50 nm.

35. The protein-carbon nanotube complex of claim 27 wherein the single-walled carbon nanotube has an S11 transition of at least 50% of background.

36. A composition comprising the protein-carbon nanotube complex of claim 27 and a pharmaceutically-acceptable carrier.

37. The composition of claim 36 comprising a plurality of protein-carbon nanotube complexes having a plurality of absorbable wavelengths.

38. The composition of claim 36 wherein at least 25% of the composition comprises a single protein-carbon nanotube complex.

39. The composition of claim 36 comprising carbon nanotubes having at least 25% of a single type of (n,m) structure.

40. The composition of claim 39 wherein the (n,m) structure is a (6,5) or (7,6) structure.