Methods and systems for treating cell proliferation disorders using plasmonics enhanced photospectral therapy (PEPST) and exciton-plasmon enhanced phototherapy (EPEP)

• US 8,951,561 B2
• Filed: 02/20/2009
• Issued: 02/10/2015
• Est. Priority Date: 08/06/2007
• Status: Active Grant

• Current Assignee: Duke University, Immunolight, LLC
• Original Assignee: Duke University, Immunolight, LLC
• Inventors: Vo-Dinh, Tuan, Bourke, Frederic A. Jr.
• Primary Examiner(s): Li, Ruixiang
• Application Number:
  US12/389,946
• Publication Number:
  US 20100003316A1
• Time in Patent Office: 2,181 Days
• US Class Current: 424/489
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 31/37 Coumarins, e.g. psoralen
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 41/0028 Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
• CPC Class Codes: A61K 41/0061 5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA
• CPC Class Codes: A61K 41/0066 Psoralene-activated UV-A photochemotherapy (PUVA-therapy), e.g. for treatment of psoriasis or eczema, extracorporeal photopheresis with psoralens or fucocoumarins
• CPC Class Codes: A61K 47/52 the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/143 with inorganic compounds
• CPC Class Codes: A61N 5/06 using light
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

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 used therein.

Claims

1. A pharmaceutical composition for treating cancer, comprising:

at least one activatable pharmaceutical agent capable of activation and of causing non-lytic cancer cell death upon activation, wherein the at least one activatable pharmaceutical agent is a psoralen or a coumarin;

at least one plasmonics-active agent capable of enhancing or modifying energy, wherein the at least one plasmonics-active agent is at least one member selected from the group consisting of gold, silver, platinum, palladium, nickel, ruthenium, rhenium, copper, and cobalt;

at least one energy modulation agent capable of activating the at least one activatable pharmaceutical agent when energized, wherein the at least one energy modulation agent is at least one member selected from the group consisting of CdS, CsCl, ZnS, Er³⁺ doped BaTiO₃, Yb³⁺ doped CsMnCl₃, CdTe, CdSe, ZnO, CdS, Y₂O₃, MgS, CaS, SrS, BaS, BaF₂, BaFBr, BaTiO₃, ZnS;

Mn,Er;

ZnSe;

Mn,Er;

MgS;

Mn,Er;

CaS;

Mn,Er;

ZnS;

Mn,Yb;

ZnSe;

Mn,Yb;

MgS;

Mn,Yb;

CaS;

Mn,Yb;

ZnS;

Tb³⁺, Er³⁺;

ZnS;

Tb³⁺;

Y₂O₃;

Tb³⁺;

Y₂O₃;

Tb³⁺, Er3⁺;

ZnS;

Mn²⁺; and

ZnS;

Mn,Er³⁺; and

a pharmaceutically acceptable carrier,

wherein the pharmaceutical composition is in a form of a plasmonics enhanced photospectral therapy (PEPST) probe comprising (a) the at least one plasmonics active agent as a plasmonics active metal nanoparticle, (b) the at least one activatable pharmaceutical agent, and (c) the at least one energy modulation agent, and has a configuration selected from the following;

the at least one activatable pharmaceutical agent bound to the at least one energy modulation agent, which is bound to the at least one plasmonics active metal nanoparticle;

the at least one plasmonics active metal nanoparticle having a nanocap formed of the at least one energy modulation agent, wherein the nanocap has attached thereto molecules of the at least one activatable pharmaceutical agent;

nanoparticles of the at least one energy modulation agent having on a surface thereof a mixture of the at least one plasmonics active metal nanoparticles and the at least one activatable pharmaceutical agent;

nanoparticles of the at least one energy modulation agent having a nanocap formed of the at least one plasmonics active metal nanoparticle, wherein the nanoparticles of the at least one energy modulation agent also have on a surface thereof molecules of the at least one activatable pharmaceutical agent;

a core formed from the at least one plasmonics active metal nanoparticle having a nanoshell formed of the at least one energy modulation agent, wherein the nanoshell has on a surface thereof molecules of the at least one activatable pharmaceutical agent;

or

at least one nanoparticle of the at least one plasmonics active metal nanoparticle attached to at least one nanoparticle of the at least one energy modulation agent, wherein the at least one nanoparticle of the at least one energy modulation agent has the at least one activatable pharmaceutical agent attached thereto by a detachable biochemical bond.

2. The pharmaceutical composition of claim 1, wherein the at least one activatable pharmaceutical agent is 8-methoxypsoralen (8-MOP) or 4′

-aminomethyl-4,5′

,8 -trimethylpsoralen (AMT).

3. The pharmaceutical composition of claim 1, wherein the non-lytic cell death is apoptosis in a target cell.

4. The pharmaceutical composition 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.

5. The pharmaceutical composition of claim 1, wherein the PEPST probe has a configuration wherein the core is formed from the at least one plasmonics active metal nanoparticle having the nanoshell formed of the at least one energy modulation agent, wherein the nanoshell has molecules of the at least one activatable pharmaceutical agent bound to the surface thereof.

6. The pharmaceutical composition of claim 5, wherein the at least one plasmonics active metal nanoparticle is a gold nanoparticle and the at least one energy modulation agent is Y₂O₃.

7. The pharmaceutical composition of claim 1, wherein the at least one plasmonics active agent is gold, the at least one energy modulation agent is Y₂O₃, and the at least one pharmaceutical agent is 8-methoxypsoralen (8-MOP).

8. A pharmaceutical composition for treating cancer, comprising:

at least one activatable pharmaceutical agent capable of activation and of causing non-lytic cancer cell death upon activation, wherein the at least one activatable pharmaceutical agent is 8-methoxypsoralen (8-MOP);

at least one plasmonics-active agent capable of enhancing or modifying energy, wherein the at least one plasmonics-active agent comprises gold;

at least one energy modulation agent capable of activating the at least one activatable pharmaceutical agent when energized, wherein the at least one energy modulation agent comprises Y₂O₃; and

a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8, wherein the non-lytic cell death is apoptosis in a target cell.

10. The pharmaceutical composition of claim 8, 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.