Tubular nanostructure targeted to cell membrane

• US 20100069606A1
• Filed: 09/15/2008
• Published: 03/18/2010
• Est. Priority Date: 09/15/2008
• Status: Active Grant

• Current Assignee: Enterprise Science Fund, LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC (Intellectual Ventures LLC)
• Inventors: Ishikawa, Muriel Y., Myhrvold, Nathan P., Tegreene, Clarence T., Jung, Edward K.Y., Wood, Lowell L. JR., Harlow, Ed, Rivet, Dennis J., Hyde, Roderick A., Sweeney, Elizabeth A., Wood, Victoria Y.H., Bangera, Mahalaxmi Gita, Leuthardt, Eric C.
• Granted Patent: US 9,187,330 B2
• Time in Patent Office: Days
• US Class Current: 530/317
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/1703 from vertebrates
• CPC Class Codes: A61K 38/1732 Lectins
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/6871 the antibody targeting an enzyme
• CPC Class Codes: A61K 47/6901 Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 40/00 Manufacture or treatment of nanostructures
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C01B 21/0648 After-treatment, e.g. grinding, purification transformation of hexagonal into cubic or wurtzitic boron nitride C04B35/5831
• CPC Class Codes: C01B 2202/02 Single-walled nanotubes
• CPC Class Codes: C01B 2202/34 Length
• CPC Class Codes: C01B 2202/36 Diameter
• CPC Class Codes: C01B 32/168 After-treatment
• CPC Class Codes: C01B 32/174 Derivatisation; Solubilisation; Dispersion in solvents
• CPC Class Codes: C01P 2004/13 Nanotubes
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10S 977/743 : having specified tube end structure, e.g. close-ended shell or open-ended tube
• CPC Class Codes: Y10S 977/75 : Single-walled
• CPC Class Codes: Y10S 977/762 : Nanowire or quantum wire, i.e. axially elongated structure having two dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/788 : Of specified organic or carbon-based composition
• CPC Class Codes: Y10S 977/795 : Composed of biological material
• CPC Class Codes: Y10S 977/848 : Tube end modifications, e.g. capping, joining, splicing
• CPC Class Codes: Y10S 977/896 : Chemical synthesis, e.g. chemical bonding or breaking
• CPC Class Codes: Y10S 977/915 : Therapeutic or pharmaceutical composition

Abstract

Devices, compositions, and methods are described which provide a tubular nanostructure targeted to a lipid bilayer membrane. The targeted tubular nanostructure can have a surface region configured to pass through a lipid bilayer membrane of a cell, a hydrophobic surface region flanked by two hydrophilic surface regions configured to form a pore in a lipid bilayer membrane of a cellular organelle, and at least one ligand configured to bind one or more cognates on the lipid bilayer membrane of the cellular organelle. The target cell can be, for example, a tumor cell, an infected cell, or a diseased cell in a subject. The tubular nanostructure can form a pore in the lipid bilayer membrane of the cellular organelle, e.g., mitochondria, which can permit transit or translocation of at least one compound across the membrane and cause cell death of the target cell.

Claims

1. A tubular nanostructure comprising:

a surface region configured to pass through a lipid bilayer membrane of a cell, and

a hydrophobic surface region flanked by two hydrophilic surface regions configured to form a pore in a lipid bilayer membrane of a cellular organelle.

2. The nanostructure of claim 1, further comprising at least one ligand configured to bind one or more cognates on the lipid bilayer membrane of the cellular organelle.

3. The nanostructure of claim 2, further comprising at least one second ligand configured to bind one or more cognates on the lipid bilayer membrane of the cell.

5. The nanostructure of claim 1, wherein the tubular nanostructure induces cell death.

6. The nanostructure of claim 1, wherein the surface region configured to pass through a lipid bilayer membrane of the cell is a hydrophobic surface region.

7. The nanostructure of claim 1, wherein the surface region configured to pass through a lipid bilayer membrane of the cell is configured to interact with a cellular component to produce the at least one tubular nanostructure including the hydrophobic surface region flanked by two hydrophilic surface regions.

8. The nanostructure of claim 7, wherein the cellular component is a cytoplasmic component.

9. The nanostructure of claim 8, wherein the cytoplasmic component is an esterase which removes a hydrophobic ester from the surface region configured to pass through a lipid bilayer membrane of the cell to produce the at least one tubular nanostructure including the hydrophobic surface region flanked by two hydrophilic surface regions.

10. The nanostructure of claim 1, wherein the nanostructure is a multi-walled nanotube including one or more outer walls configured as the surface region to pass through a lipid bilayer membrane of the cell, and one or more inner walls including the hydrophobic surface region flanked by two hydrophilic surface regions configured to form a pore in a lipid bilayer membrane of a cellular organelle.

11. The nanostructure of claim 10, wherein the surface region to pass through a lipid bilayer membrane of the cell is a hydrophobic surface region or a structured amphiphilic surface region.

12. The nanostructure of claim 1, wherein the cell is a neoplastic cell, an infected cell, a bacterial cell, or a parasite cell.

13. The nanostructure of claim 1, wherein the nanostructure includes one or more of a carbon nanotube, cyclic peptide nanotube, crown ether nanotube, polymer nanotube, polymer/carbon nanotube, DNA nanotube, or inorganic nanotube.

17. The nanostructure of claim 13, wherein the hydrophobic surface region includes a single wall carbon nanotube surface region.

18. The nanostructure of claim 1, wherein the hydrophilic surface region includes one or more of amines, amides, charged or polar amino acids, alcohols, carboxylic groups, oxides, ester groups, ether groups, or ester-ether groups, ketones, aldehydes, or derivatives thereof.

19. The nanostructure of claim 2, wherein the one or more cognates is one or more cell surface receptors or cell surface markers in the lipid bilayer membrane.

20. The nanostructure of claim 2, wherein the one or more cognates include at least one of a protein, a carbohydrate, a glycoprotein, a glycolipid, a sphingolipid, a glycerolipid or a metabolite thereof.

21. The nanostructure of claim 3, wherein the one or more cognates is one or more cell surface receptors or cell surface markers in the lipid bilayer membrane.

22. The nanostructure of claim 3, wherein the one or more cognates include at least one of a protein, a carbohydrate, a glycoprotein, a glycolipid, a sphingolipid, a glycerolipid or a metabolite thereof.

23. The nanostructure of claim 1, wherein one or both of the hydrophilic surface regions are at the end of the nanostructure.

24. The nanostructure of claim 1, having a length of about 1 nm to about 1500 nm.

25. The nanostructure of claim 1, having a diameter of about 0.5 nm to about 5 nm.

26. The nanostructure of claim 24, having a length of about 20 Å

to about 40 Å

.

27. The nanostructure of claim 25, having a diameter of about 5 Å

to about 20 Å

.

28. The nanostructure of claim 2, wherein the at least one ligand is at least a portion of an antibody, antibody-coated liposome, polynucleotide, polypeptide, receptor, viral plasmid, polymer, small chemical compound, carbohydrate, lipid, toxin, pore-forming toxin, or lectin.

29. The nanostructure of claim 28, wherein the at least one ligand is a therapeutic compound configured to treat a disease, condition, or symptom.

30. The nanostructure of claim 3, wherein the at least one second ligand is at least a portion of an antibody, antibody-coated liposome, polynucleotide, polypeptide, receptor, viral plasmid, polymer, small chemical compound, carbohydrate, lipid, toxin, pore-forming toxin, or lectin.

31. The nanostructure of claim 30, wherein the at least one second ligand is a therapeutic compound configured to treat a disease, condition, or symptom.

32. The nanostructure of claim 1, further comprising one or more elements to control transport of molecules through the tubular nanostructure.

33. The nanostructure of claim 32, wherein the one or more elements control transport of molecules into the cellular organelle.

34. The nanostructure of claim 32, wherein the one or more elements control transport of molecules out of the cellular organelle.

35. The nanostructure of claim 32, wherein the one or more elements includes a hydrophilic inner liner of the tubular nanostructure.

36. The nanostructure of claim 32, wherein the one or more elements includes at least one ligand configured to reversibly bind a cognate of interest, wherein the cognate of interest passes through the pore.

37. The nanostructure of claim 36, wherein the at least one ligand includes a monospecific antibody or a bispecific antibody.

38. The nanostructure of claim 32, wherein the one or more elements reversibly blocks the pore.

39. The nanostructure of claim 38, wherein the one or more elements is a magnetic entity.

40. The nanostructure of claim 38, wherein the one or more elements is a molecular entity.

41. The nanostructure of claim 40, wherein the molecular entity is at least a portion of a carbon nanostructure, polynucleotide, polypeptide, antibody, receptor, glycoprotein, lipid, polysaccharide, or polymer.

42. The nanostructure of claim 32, wherein the one or more elements includes a charged group.

43. The nanostructure of claim 32, wherein the one or more elements are passive.

44. The nanostructure of claim 32, wherein the one or more elements are active.

45. The nanostructure of claim 44, wherein the one or more active elements includes at least one of an ATPase transport element, Na+K+ ATPase, H+K+ ATPase, or Ca2+ ATPase.

46. The nanostructure of claim 44, wherein the one or more active elements includes at least one of an ABC transporter element, CFTR transporter, TAP transporter, or liver cell transporter.

47. The nanostructure of claim 44, wherein the one or more active elements includes at least one of a symport pump, Na+/iodide transporter, E. coli permease, or an antiport pump.

48. The nanostructure of claim 1, wherein the pore permits transit or translocation of at least one compound across the membrane of the cellular organelle.

49. The nanostructure of claim 1, further comprising a marker attached to the nanostructure.

50. The nanostructure of claim 49, wherein the marker includes a fluorescent marker, a radioactive marker, quantum dot, metal, or magnetic resonance imaging marker.

51. The nanostructure of claim 49, wherein the marker is activated by anchoring in the membrane of the cellular organelle.

52. The nanostructure of claim 51, wherein the marker is activated by a ligand reaction.

53. The nanostructure of claim 51, wherein the marker is activated by interaction with a hydrophobic medium.

54. The nanostructure of claim 1, wherein the hydrophobic surface region is extended in diameter.

55. The nanostructure of claim 54, wherein the hydrophobic surface region is extended in diameter by a disk, a stub, or a graphene sheet.

56. The nanostructure of claim 1, wherein the nanostructure anchors in the membrane of the cell organelle.

57. The nanostructure of claim 1, wherein the surface region is configured to match a configuration of the lipid bilayer membrane of the cell organelle.

58. The nanostructure of claim 1, wherein the organelle is a mitochondria.

102. The nanostructure of claim 1, wherein the surface region configured to pass through a lipid bilayer membrane of the cell is a structured amphiphilic surface region.

4. (canceled)

14-16. -16. (canceled)

59-101. -101. (canceled)