Particles for the treatment of cancer in combination with radiotherapy

• US 10,137,149 B2
• Filed: 12/08/2010
• Issued: 11/27/2018
• Est. Priority Date: 12/09/2009
• Status: Active Grant

• Current Assignee: Oxford University Innovation Limited (University of Oxford)
• Original Assignee: Oxford University Innovation Limited (University of Oxford)
• Inventors: Dobson, Peter James, Wakefield, Gareth, Townley, Helen Elizabeth
• Primary Examiner(s): Browe, David
• Application Number:
  US13/514,487
• Publication Number:
  US 20120282185A1
• Time in Patent Office: 2,911 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/244 Lanthanides; Compounds thereof medicinal preparations containing radioactive lanthanides for use in therapy or testing in vivo A61K51/00
• CPC Class Codes: A61K 41/0038 Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy radiotherapy per se A61N5/10
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The invention provides a particle comprising a metal oxide which is doped with at least one rare earth element, wherein the metal oxide is selected from titanium dioxide, zinc oxide, cerium oxide and mixtures of two or more thereof. The invention also provides a pharmaceutical composition comprising the particles, and to uses of the particles and composition in the treatment and diagnosis of cancer.

Claims

1. A method of treating cancer in a subject comprising:

administering a particle to a locus or site of the cancer or to tumour tissue in the subject, which particle comprises a metal oxide, which metal oxide is titanium dioxide doped with from 0.1 to 25 mol % of at least one rare earth element, wherein the titanium dioxide is a host lattice and the at least one rare earth element is present as a dopant within said host lattice; and

applying X-ray radiation suitable for radiotherapy to the locus or site of the cancer or tumour tissue and thereby exciting the metal oxide in the particle at the locus or site of the cancer or tumour tissue and generating reactive oxygen species at the locus or site of the cancer or tumour tissue.

2. The method according to claim 1, wherein the particle comprises a core consisting of titanium dioxide doped with from 0.1 to 25 mol % of at least one rare earth element.

3. The method according to claim 1, wherein the metal oxide is doped with at least two different rare earth elements.

4. The method according to claim 1, wherein the metal oxide is doped with gadolinium.

5. The method according to claim 1 wherein the metal oxide is doped with europium.

6. The method according to claim 1 wherein the metal oxide is doped with erbium.

7. The method according to claim 1 wherein the metal oxide is doped with neodymium.

8. The method according to claim 1, wherein the particle has a size of less than 400 nm.

9. The method according to claim 1, wherein the particle has a coating comprising silica, alumina, polyethylene glycol, polystyrene, a saccharide, an oligosaccharide, a polysaccharide or a mixture of two or more thereof.

10. The method according to claim 9 wherein a targeting moiety is attached to the coating.

11. The method according to claim 9, wherein an optical contrast agent, a radioisotope, a paramagnetic contrast agent or a superparamagnetic contrast agent is attached to the coating.

12. The method according to claim 1 wherein the cancer is a cancer of the lung, liver, kidney, bladder, breast, head, neck, brain, ovaries, prostate, intestine, colon, rectum, uterus, pancreas, eye, bone marrow, lymphatic system or thyroid gland.

13. The method according to claim 1 comprising:

(a) administering the particle by intra-tumoral injection into the tumour tissue or at the cancer site or locus;

or

(b) parenterally administering to the subject the particle and allowing the particle to localize at the locus or site of the cancer or tumour tissue.

14. The method according to claim 1 further comprising the step of detecting the presence of the particle at the locus or site of the cancer or tumour tissue before directing X-ray radiation to the locus or site of the cancer or tumour tissue.

16. A method according to claim 1, wherein the host lattice is substitution doped or interstitial doped with the at least one rare earth element.

17. A method according to claim 1, wherein the host lattice is substitution doped with the at least one rare earth element.

15. An in vitro method of destroying cancer cells comprising adding a particle to a cell culture, medium or solution comprising cancer cells, then directing X-ray radiation at the cancer cells, wherein the particle comprises a metal oxide, which metal oxide is titanium dioxide and is doped with from 0.1 to 25 mol % of at least one rare earth element, and wherein the titanium dioxide is a host lattice and the at least one rare earth element is present as a dopant within said host lattice.