Thermotherapy via targeted delivery of nanoscale magnetic particles

• US 7,074,175 B2
• Filed: 06/18/2002
• Issued: 07/11/2006
• Est. Priority Date: 07/25/2001
• Status: Expired due to Fees

• Current Assignee: Aspen Medisys, LLC (Rhinomed Ltd.)
• Original Assignee: Triton Biosystems Inc (Novartis Ag)
• Inventors: Ellis-Busby, Diane, Foreman, Allan, Ivkov, Robert, Handy, Erik Schroeder
• Primary Examiner(s): Lacyk, John P.
• Application Number:
  US10/176,950
• Publication Number:
  US 20030028071A1
• Time in Patent Office: 1,484 Days
• Field of Search: 600 9- 15, 607/103, 607/105, 424422-423, 424/426, 424/428, 424/430, 424434-437, 424489-491, 424493-502, 424647-648, 424/1.29, 424/1.33, 424/1.53, 424 932- 9323, 977/DIG.1
• US Class Current: 600/9
• CPC Class Codes: A61N 1/406 using implantable thermoseeds or injected particles for localized hyperthermia preparations of seeds and particles A61K41/0052
• CPC Class Codes: A61N 2/02 using magnetic fields produced by coils, including single turn loops or electromagnets A61N2/12 takes precedence
• CPC Class Codes: Y10S 977/902 Specified use of nanostructure

Abstract

Disclosed are compositions comprising magnetic nanoparticles, a biocompatible coating, and a target-specific ligand. Also disclosed are devices for treating diseased tissue for use with such compositions. Further disclosed are methods for treating diseased tissue, such as cancer, using such compositions and devices, as well as methods for treating diseased tissue utilizing hypertermia.

Claims

1. A magnetic material composition, comprising:

a) a single domain magnetic particle capable of being heated by Neé

l relaxation in response to an alternating magnetic field;

b) a biocompatible coating material for the particle; and

c) a ligand selective to at least one cancer marker on a cell in cancer tissue, the ligand being i) bound to an uncoated portion of the particle, ii) bound to a coated portion of the particle, iii) bound to the particle and partially covered by the coating, or iv) intercalated into the coating.

2. A magnetic particle composition of claim 1, wherein the particle has a size of no more than 250 nm in at least one dimension.

3. A magnetic material composition of claim 1, wherein the particle, the coating and the ligand are suspended in a biologically compatible fluid.

4. A magnetic material composition of claim 1, wherein the magnetic particle has a Curie temperature in the range of about 40°

C. to about 150°

C.

5. A magnetic material composition of claim 1, wherein the magnetic particle is formed of a biocompatible material, the surface of the magnetic particle forming the biocompatible coating.

6. A magnetic material composition of claim 1, wherein the biocompatible coating material is one of an organic material, an inorganic material, and a combination of an inorganic material and an organic material.

7. A magnetic material composition of claim 6, wherein the organic material is at least one of a synthetic material and a biological material.

8. A magnetic material composition of claim 7, wherein the synthetic material is a polymer, a copolymer, or a combination thereof.

9. A magnetic material composition of claim 7, wherein the synthetic material is selected from the group consisting of i) a polymer, ii) a copolymer, and iii) a polymer blend formed from a polymer based on at least one of acrylates, styrenes, acetates, alkylene glycols, alkylenes, alkylene oxides, parylene, lactic acid, and glycolic acid.

10. A magnetic material composition of claim 7, wherein the synthetic material is selected from the group consisting of i) a hydrogel polymer, ii) a histidine-containing polymer, iii) a surfactant, and iv) a combination of at least one of i)–

iii).

11. A magnetic material composition of claim 7, wherein the biological material is selected from the group consisting of i) a polysaccharide, ii) a polyaminoacid, iii) a protein, iv) a lipid, v) a glycerol, vi) a fatty acid, and vii) a combination including at least one of i)–

vi).

12. A magnetic material composition of claim 11, wherein the polysaccharide is selected from the group consisting of a) a heparin, b) heparin sulfate, c) chondroitin sulfate, d) chitin, e) chitosan, f) cellulose, g) dextran, h) alginate, i) starch, j) saccharide, k) carbohydrate, l) glycosaminoglycan, and m) a combination of any of a)–

l).

13. A magnetic material composition of claim 11, wherein the protein is selected from the group consisting of a) an extracellular matrix protein, b) proteoglycan, c) glycoprotein, d) albumin, e) peptide, f) gelatin, and g) a combination of any of a)–

f).

14. A magnetic material composition of claim 6, wherein the inorganic material is selected from the group consisting of i) a metal, ii) a metal alloy, iii) a ceramic, iv) an oxide of a Group IV element, and v) a combination of any of i)–

iv).

15. A magnetic material composition of claim 14, wherein the ceramic is selected from the group consisting of a) hydroxyapatite, b) silicon carbide, c) carboxylate, d) sulfonate, e) phosphate, f) ferrite, g) phosphonate, and h) a combination of any of a)–

g).

16. A magnetic material composition of claim 7, wherein the biological material is a transfection agent to enhance uptake by cancer cells.

17. A magnetic material composition of claim 16, wherein the transfection agent is selected from the group consisting of i) a vector, ii) a prion, iii) a polyaminoacid, iv) a cationic liposome, v) an amphiphile, vi) a non-liposomal lipid, and vii) a combination of any of i)–

vi).

18. A magnetic material composition according to claim 17, wherein the vector is selected from the group consisting of a) a plasmid, b) a virus, c) a phage, d) a viron, e) a viral coat, and f) a combination of any of a)–

e).

19. A magnetic material composition of claim 17, wherein the polyaminoacid is a poly L-lysine.

20. A magnetic material composition of claim 7, wherein the synthetic material is a transfection agent.

21. A magnetic material composition of claim 20, wherein the transfection agent is selected from the group consisting of i) a non-lipid cationic polymer, ii) a dendrimer, iii) polyethyleneimine, and iv) a combination of any of i)–

iii).

22. A magnetic material composition of claim 1, wherein the ligand is one of a molecule and a combination of molecules selective to at least one specific cancer marker.

23. A magnetic material composition of claim 22, wherein the molecule is selected from the group consisting of i) a saccharide, ii) a carbohydrate, iii) a glycan, iv) a protein, v) a peptide, vi) an antibody, vii) an antibody fragment, viii) a receptor, ix) a Cluster Designation/Differentiation (CD) marker, x) a cytokine, xi) a chemokine, xii) a nucleotide, xiii) a lipid, xiv) a steroid, xv) a neurotransmitter, xvi) a lectin, xvii) an imprinted polymer, xviii) an oncogene, xix) an oncogene receptor, and xx) a combination of any of i)–

xix).

24. A magnetic material composition of claim 23, wherein the protein is selected from the group comprising a) a membrane protein, b) a proteoglycan, c) a cell surface protein, d) a glycoprotein, and e) a combination of any of a)–

d).

25. A magnetic material composition of claim 23, wherein the antibody is selected from the group consisting of a) a polyclonal antibody, b) a monoclonal antibody, c) a chimeric antibody, d) a humanized antibody, e) a human antibody, f) a recombinant antibody, g) a bispecific antibody, h) an antibody fragment, i) a recombinant single chain antibody fragment and j) a combination of any of a–

i).

26. A magnetic material composition of claim 23, wherein the nucleotide is selected from the group consisting of a) a complete nucleotide, b) a nucleotide fragment, c) a complementary nucleotide, and d) a combination of a)–

c).

27. A magnetic material composition of claim 23, wherein the lipid includes a) a phospholipid, b) a glycolipid, or c) a combination of a) and b).

28. A magnetic material composition of claim 22, wherein the marker is specific to breast cancer.

29. A magnetic material composition of claim 27, wherein the marker is specific to a metastatic cancer related to breast cancer.

30. A magnetic material composition of claim 27, wherein the marker is specific to a primary cancer of the breast.

31. A magnetic material composition of claim 27, wherein the breast cancer-specific marker is selected from the group consisting of a) a member of the MUC-type mucin family, b) a member of the epidermal growth factor receptor (EGFR) family, c) a carcinoembryonic antigen (CEA), d) a MAGE (melanoma antigen) gene family antigen, e) a T/Tn antigen, f) a hormone receptor, g) a Cluster Designation/Differentiation (CD) antigen, h) a tumor suppressor gene, i) a cell cycle regulator, j) an oncogene, k) an oncogene receptor, l) a proliferation marker, m) an adhesion molecule, n) a proteinase involved in degradation of extracellular matrix, o) a malignant transformation related factor, p) an apoptosis related factor, q) a human carcinoma antigen, r) a member of the vascular endothelial growth factor (VEGF) receptor family, s) glycoprotein antigens, t) DF3 antigen, u) 4F2 antigen, v) MFGM antigen, and w) a combination of any of a) through v).

32. A magnetic material composition of claim 31, wherein the MUC-type mucin family marker is MUC-1.

33. A magnetic material composition of claim 31, wherein the EGFR is selected from the group consisting of at least one of Her-1, Her-2, Her-3, Her-4, and any combination thereof.

34. A magnetic material composition of claim 1, further comprising a linking agent linking between the ligand and the magnetic particle or between the ligand and the biocompatible coating material.

35. A magnetic material composition of claim 33, wherein the linking agent links to at least one of i) an amine group, ii) a sulfhydryl group, iii) a carbohydrate group, iv) a carboxyl group, v) a hydroxyl group, and vi) a combination of any of i)–

v).

36. A magnetic material composition of claim 33, wherein the linking agent is comprised of at least one of i) homobifunctional crosslinkers, ii) heterobifunctional crosslinkers, iii) aldehydes, iv) homotrifunctional crosslinkers, v) heterotrifunctional crosslinkers, and a combination of any of i)–

v).

37. A method for treating cancer in a patient, comprising:

a) administering the magnetic material composition of claim 1 to the patient; and

b) applying an alternating magnetic field to a region of the patient containing the cancer so as to inductively heat the magnetic material composition.

38. A method according to claim 37, further comprising inducing cancer cell death by the inductively heated magnetic material via necrosis or apoptosis.

39. A method according to claim 38, further comprising applying the alternating magnetic field to a region of the patient containing cancer tissue and to a region of the patient adjacent to the region containing the cancer tissue.

40. A method according to claim 37, further comprising applying a static magnetic field to a region of the patient containing cancer tissue to aid in localizing the magnetic material composition to the region containing the cancer tissue.

41. A method according to claim 37, further comprising monitoring at least one physical characteristic of at least one of cancer tissue and non-cancer tissue.

42. A method according to claim 41, wherein monitoring the at least one physical characteristic includes monitoring temperature.

43. A method according to claim 41, wherein monitoring the at least one physical characteristic includes monitoring tissue impedance.

44. A method according to claim 37, wherein the alternating magnetic field is applied to the patient over a treatment duration, and applying the alternating magnetic field includes pulsing the alternating magnetic field to have a pulse length less than the treatment duration.

45. A method according to claim 44, further comprising applying at least two pulses of alternating magnetic field to the patient.

46. A method according to claim 37, wherein administering the magnetic material composition includes injecting the magnetic material composition into the patient.

47. A method according to claim 37, further comprising a magnetic field generator that generates the alternating magnetic field, wherein the alternating magnetic field has a strength in the range of about 100 to about 2,000 Oe in the region of the patient containing the cancer.

48. A method according to claim 47, wherein the alternating magnetic field has a triangular waveform.

49. A method according to claim 37, wherein applying the alternating magnetic field includes modulating the alternating magnetic field.

50. A method according to claim 49, wherein modulating the magnetic field includes applying a modulation having one of a sinusoidal envelope, a triangular envelope, a square wave envelope, a trapezoidal envelope, and a sawtooth envelope.

51. A method for treating cancer in a patient, comprising:

a) administering to the patient a magnetic material composition of claim 1; and

b) applying an alternating magnetic field to a region of the patient containing the cancer such that the magnetic material composition inductively heats, wherein the alternating magnetic field is applied using a device comprising;

i) a magnetic generator having a core defining at least part of a magnetic circuit, two poles of the core defining a gap therebetween, a magnetic field passing between two poles, the gap being of sufficient size to receive a portion of the patient containing the cancer cells; and

ii) a power supply coupled to provide energy to the magnetic generator so that the magnetic field passing between the two poles alternates at a frequency in the range from about 1 kHz to about 1 GHz,

wherein the alternating magnetic field strength is in the range from about 10 Oe to about 10,000 Oe.

52. A method according to claim 51, wherein the magnetic material composition inductively heats to a sufficient temperature to induce cancer cell death.

53. A method according to claim 51, further comprising inducing cancer cell death by inductively heated magnetic material via necrosis, apoptosis or another mechanism.

54. A method according to claim 51, further comprising applying the alternating magnetic field to a region of the patient containing cancer tissue and to a region of the patient adjacent the region containing the cancer tissue.

55. A method according to claim 51, further comprising applying a static magnetic field to a region of the patient containing cancer tissue to aid in localizing the magnetic material composition to the region containing the cancer tissue.

56. A method according to claim 51, further comprising monitoring at least one physical characteristic of at least one of cancer tissue and non-cancer tissue while applying the alternating magnetic field.

57. A method according to claim 51, further comprising pulsing the alternating magnetic field while applying the alternating magnetic field.

58. A method according to claim 57, further comprising exposing the patient to at least two pulses of the alternating magnetic field while applying the alternating magnetic field.