Advanced methods and systems for treating cell proliferation disorders

Patent metadata

Field	Value
Publication number	US-9833634-B2
Application number	US-201414256550-A
Country	US
Kind code	B2
Filing date	Apr 18, 2014
Priority date	Jul 14, 2008
Publication date	Dec 5, 2017
Grant date	Dec 5, 2017

Abstract

The present invention relates to methods for treating cell proliferation disorders comprising (1) administering to the subject at least one activatable pharmaceutical agent that is capable of activation by a simultaneous two photon absorption event and of effecting a predetermined cellular change when activated, (2) administering at least one plasmonics-active agent to the subject, and (3) applying an initiation energy from an initiation energy source to the subject, wherein the plasmonics-active agent enhances or modifies the applied initiation energy, such that the enhanced or modified initiation energy activates the activatable pharmaceutical agent by the simultaneous two photon absorption event in situ, thus causing the predetermined cellular change to occur, wherein said predetermined cellular change treats the cell proliferation related disorder, and the use of plasmonics enhanced photospectral therapy (PEPST) and exiton-plasmon enhanced phototherapy (EPEP) in the treatment of various cell proliferation disorders, and the PEPST and EPEP agents and probes.

First claim

The invention claimed is:

1. A method for treating a cell proliferation disorder in a subject, comprising:
(1) administering to the subject at least one energy modulation agent, at least one activatable pharmaceutical agent that is capable of activation by a simultaneous two photon absorption event and of inducing a predetermined cellular change in a target cell in the subject when activated, and a carrier for delivery of the at least one activatable pharmaceutical agent;
(2) administering at least one plasmonics-active agent that enhances or modifies energy to the subject;
(3) applying an initiation energy from an initiation energy source to the subject;
wherein
(A) the energy modulation agent upgrades or downgrades the applied initiation energy, and wherein the plasmonics-active agent enhances or modifies the upgraded or downgraded energy, such that the enhanced or modified upgraded or downgraded energy activates the activatable pharmaceutical agent by the simultaneous two photon absorption event in situ, and/or
(B) the plasmonics-active agent enhances or modifies the applied initiation energy, such that the enhanced or modified initiation energy excites the modulation agent which upgrades or downgrades the enhanced or modified initiation energy to an energy that activated the activatable pharmaceutical agent by the simultaneous two photon absorption event in situ,
wherein the predetermined cellular change is apoptosis in a target cell, and
wherein the at least one activated pharmaceutical agent reacts with a target cell and causes an auto-vaccine effect in the subject, thereby treating the cell proliferation disorder.

2. The method of claim 1 , wherein said predetermined cellular change treats the cell proliferation disorder by causing an increase or decrease in cell proliferation rate of a target cell.

3. The method of claim 1 , wherein the initiation energy source is selected from the group consisting of UV radiation, visible light, infrared radiation, x-rays, gamma rays, electron beams, phosphorescent compounds, chemiluminescent compounds, bioluminescent compounds, and light emitting enzymes.

4. The method of claim 1 , wherein the initiation energy source is a source of lower energy than UV-A, visible energy, and IR or NRI energy, and said at least one energy modulation agent converts the initiation energy to UV-A, visible or near infrared energy, wherein the modulation agent upgrades energy.

5. The method of claim 1 , wherein the initiation energy source is a source of higher energy than UV-A or visible energy and said at least one energy modulation agent converts the initiation energy into UV-A or visible energy, wherein the modulation agent downgrades energy.

6. The method of claim 1 , wherein the initiation energy is an IR energy, and the energy activating the activatable agent is not UVA or visible light energy.

7. The method of claim 1 , wherein the at least one energy modulation agent is one or more selected from the group consisting of a biocompatible fluorescing metal nanoparticle, fluorescing dye molecule, gold nanoparticle, a water soluble quantum dot encapsulated by polyamidoamine dendrimers, a luciferase, a biocompatible phosphorescent molecule, a combined electromagnetic energy harvester molecule, and a lanthanide chelate capable of intense luminescence.

8. The method of claim 1 , wherein the initiation energy is applied via a thin fiber optic.

9. The method of claim 1 , wherein the cell proliferation disorder is at least one member selected from the group consisting of cancer, bacterial infection, viral infection, immune rejection response, autoimmune disorders, aplastic conditions, and combinations thereof.

10. The method of claim 1 , wherein the at least one activatable pharmaceutical agent is a photoactivatable agent.

11. The method of claim 1 , wherein the at least one activatable pharmaceutical agent is selected from psoralens, pyrene cholesteryloleate, acridine, porphyrin, fluorescein, rhodamine, 16-diazorcortisone, ethidium, transition metal complexes of bleomycin, transition metal complexes of deglycobleomycin organoplatinum complexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites, vitamin precursors, naphthoquinones, naphthalenes, naphthols and derivatives thereof having planar molecular conformations, porphorinporphyrins, dyes and phenothiazine derivatives, coumarins, quinolones, quinones, and anthroquinones.

12. The method of claim 10 , wherein the at least one activatable pharmaceutical agent is 8-MOP or AMT.

13. The method of claim 11 , wherein the at least one activatable pharmaceutical agent is a psoralen, a coumarin, a porphyrin, or a derivative thereof.

14. The method of claim 1 , wherein the at least one activatable pharmaceutical agent is one selected from 7,8-dimethyl-10-ribityl, isoalloxazine, 7,8,10-trimethylisoalloxazine, 7,8-dimethylalloxazine, isoalloxazine-adenine dinucleotide, alloxazine mononucleotide, aluminum (III) phthalocyanine tetrasulonate, hematophorphyrin, and phthalocyanine.

15. The method of claim 1 , wherein the at least one activatable pharmaceutical agent is coupled to the carrier that is capable of binding to a receptor site.

16. The method of claim 15 , wherein the carrier is one selected from insulin, interleukin, thymopoietin or transferrin.

17. The method of claim 15 , wherein the at least one activatable pharmaceutical agent is coupled to the carrier by a covalent bond.

18. The method of claim 15 , wherein the at least one activatable pharmaceutical agent is coupled to the carrier by non-covalent bond.

19. The method of claim 15 , wherein the receptor site is one selected from nucleic acids of nucleated cells, antigenic sites on nucleated cells, or epitopes.

20. The method of claim 1 , wherein the at least one activatable pharmaceutical agent has affinity for a target cell.

21. The method of claim 1 , wherein the at least one activatable pharmaceutical agent is capable of being preferentially absorbed by a target cell.

22. The method of claim 1 , wherein the auto-vaccine effect is generated in a joint or lymph node.

23. The method of claim 1 , wherein the at least one activatable pharmaceutical agent is a DNA intercalator or a halogenated derivative thereof.

24. The method of claim 1 , wherein the initiation energy is one of electromagnetic energy, acoustic energy, or thermal energy.

25. The method of claim 1 , further comprising a blocking agent, wherein the blocking agent is capable of blocking uptake of the at least one activatable pharmaceutical agent prior to its activation.

26. The method of claim 25 , wherein the blocking agent is capable of slowing down mitosis in non-target cells while allowing target cells to maintain an abnormal rate of mitosis.

27. The method of claim 1 , wherein said at least one energy modulation agent is a single energy modulation agent, and is coupled to said at least one activatable pharmaceutical agent.

28. The method of claim 1 , wherein a plurality of the energy modulation agents is administered, and wherein the enhanced or modified initiation energy or the enhanced or modified initiation energy is converted, through a cascade energy transfer between the plurality of the energy modulation agents, to an energy that activates the at least one activatable pharmaceutical agent.

29. The method of claim 1 , wherein the at least one ac

Assignees

• Immunolight Llc
• Univ Duke

Inventors

• Bourke Frederic A
• Vo Dinh Tuan

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/55

  the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug · CPC title

• A61N5/062 Primary

  Photodynamic therapy, i.e. excitation of an agent · CPC title

• A61K47/551

  one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid · CPC title

• A61K31/7056

  containing five-membered rings with nitrogen as a ring hetero atom · CPC title