Method And Dyes For Detecting And Destroying Cancer Cells

Abstract

This invention relates to new carbocyanine dye compositions, pharmaceutical compositions comprising such compositions, methods of detecting via near infrared fluorescent imaging incipient cancer cells and selective destruction of cancer cells identified by administration of such pharmaceutical compositions. A method of detecting and destroying cancer cells includes introducing a gold dye into an organism suspected of having a cancer cell. The gold dye is a carbocyanine dye covalently attached to a gold nanoparticle. A near infrared light is shined on a region suspected of having the cancer cell. Fluorescence from the gold dye is detected. A beam of radio frequency energy is directed at the region to induce hyperthermia in the cancer cell. The carbocyanine dye has the most basic structure of MHI-148 and structures 6 and 22 with a Au n —[S—CH 2 (CH 2 ) 9 CH 2 —(OCH 2 CH 2 ) 4 O]COCH 2 CH 2 -phenyl-O group on a cyclohexene ring that imparts activity to the cancer cell binding and destruction processes.

What is claimed is: 
     
         1 . A method of detecting and destroying cancer cells, comprising the steps of:
 introducing a gold dye into an organism suspected of having a cancer cell, wherein the gold dye is a carbocyanine dye covalently attached to a metal nanoparticle;   shinning a near infrared light on a region suspected of having the cancer cell;   detecting a fluorescence from the gold dye;   targeting a beam of radio frequency energy at the region to induce hyperthermia in the cancer cell.   
     
     
         2 . The method of  claim 1 , further including the step of not inducing hyperthermia in non-cancer cells near the cancer cell. 
     
     
         3 . The method of  claim 1 , wherein the step of introducing the gold dye includes attaching the metal nanoparticle by an Au n —[S—CH2(CH2)9CH2-(OCH2CH2)4O]COCH2CH2-phenyl-O group on a cyclohexene ring of the carbocyanine dye. 
     
     
         4 . The method of  claim 3 , further including synthesizing the carbocyanine dye represented by Formula 1. 
     
     
         5 . The method of  claim 4 , wherein the gold nanoparticle is attached to a cyclohexene ring of the carbocyanine dye. 
     
     
         6 . The method of  claim 1 , wherein the step of shinning the near infrared light includes the step of selecting a GaAlAs diode laser with a predetermined wavelength. 
     
     
         7 . A heptamethine cyanine dye covalently attached to a metal particle having a maximum absorption wavelength in the region between 780 and 1100 nm. 
     
     
         8 . The heptamethine cyanine dye of  claim 7 , wherein the heptamethine cyanine dye is represented by Formula 1. 
     
     
         9 . The heptamethine cyanine dye of  claim 7 , wherein the heptamethine cyanine dye is represented by Formula 2. 
     
     
         10 . The heptamethine cyanine dye of  claim 7 , wherein the heptamethine cyanine dye is represented by Formula 3. 
     
     
         11 . The heptamethine cyanine dye of  claim 7 , wherein the heptamethine cyanine dye is represented by Formula 4. 
     
     
         12 . The heptamethine cyanine dye of  claim 7 , wherein the heptamethine cyanine dye is represented by Formula 5. 
     
     
         13 . The heptamethine cyanine dye of  claim 7 , wherein the heptamethine cyanine dye is represented by Formula 6. 
     
     
         14 . The heptamethine cyanine dye of  claim 7 , wherein the heptamethine cyanine dye is represented by Formula 7. 
     
     
         15 . The heptamethine cyanine dye of  claim 7 , wherein the heptamethine cyanine dye is represented by Formula 8. 
     
     
         16 . The heptamethine cyanine dye of  claim 7 , wherein the bromide counter anions are replaced with an pharmaceutically acceptable carrier. 
     
     
         17 . The heptamethine cyanine dye of  claim 7 , wherein the bromide counter anions are replaced with an pharmaceutically acceptable excipient. 
     
     
         18 . An unsymmetrical cyanine dye with a covalently attached to a metal particle as represented in Formula 9 having a maximum absorption wavelength in the region between 680 to 760 nm. 
     
     
         19 . The unsymmetrical cyanine dye of  claim 18 , wherein the unsymmetrical cyanine dye is a tricarbocyanine. 
     
     
         20 . The unsymmetrical cyanine dye of  claim 18 , wherein the unsymmetrical cyanine dye is a pentacarbocyanine. 
     
     
         21 . The unsymmetrical cyanine dye of  claim 18 , wherein the unsymmetrical cyanine dye is a heptacarbocyanine. 
     
     
         22 . A symmetrical cyanine dye of the structure 6. 
     
     
         23 . A symmetrical cyanine dye of the structure 22. 
     
     
         24 . A symmetrical cyanine dye of structure 6 attached to a functionalized gold nanoparticle AuS—[CH2]9-(OCH2CH2)4OH via an ester bond. 
     
     
         25 . A symmetrical cyanine dye of structure 6 attached to a functionalized gold nanoparticle Au—S—[CH2]9NH2 via an amide bond. 
     
     
         26 . A symmetrical cyanine dye of structure 6 attached to a functionalized gold nanoparticle Au—S—[CH2]9-SH via a thioester bond 
     
     
         27 . A symmetrical cyanine dye of structure 22 attached to a functionalized gold nanoparticle AuS—[CH2]9-(OCH 2 CH 2 )4OH via an ester bond. 
     
     
         27 . A symmetrical cyanine dye of structure 22 attached to a functionalized gold nanoparticle Au—S—[CH2]9NH2 via an amide bond. 
     
     
         28 . A symmetrical cyanine dye of formula 22 attached to a functionalized gold nanoparticle Au—S—[CH2]9-SH via a thioester bond. 
     
     
         29 . A symmetrical cyanine dye of structure 6 or 22 in which the O-phenyl-CH2CH2CO2H group is replaced by S[CH2]9S—Au n . 
     
     
         30 . A method of detecting and destroying cancer cells, comprising:
 introducing a composition into an organism suspected of having cancer cells;
 wherein said composition comprises a carbocyanine dye covalently attached to a metal nanoparticle via a linker bound to a cyclohexene ring or a cyclopentene ring of said carbocyanine dye; 
 wherein said linker comprises a polyethylene group; and 
 wherein said composition selectively binds to said cancer cells; 
   shining a near infrared light on a region suspected of having said cancer cells;   detecting a fluorescence from said composition to locate said cancer cells; and   targeting a beam of radio frequency energy at said region to induce hyperthermia in said cancer cells.   
     
     
         31 . The method of  claim 30 , wherein said fluorescence is emitted by said carbocyanine dye. 
     
     
         32 . The method of  claim 30 , wherein said composition does not bind to healthy cells. 
     
     
         33 . The method of  claim 30 , wherein said carbocyanine dye absorbs light having a wavelength ranging from between about 680 nanometers to about 1200 nanometers. 
     
     
         34 . The method of  claim 30 , wherein said carbocyanine dye comprises a heptamethine cyanine dye. 
     
     
         35 . The method of  claim 34 , wherein said heptamethine cyanine dye absorbs light having a wavelength ranging from between about 780 nanometers to about 1100 nanometers. 
     
     
         36 . The method of  claim 30 , wherein said induction of hyperthermia is facilitated by said metal nanoparticle. 
     
     
         37 . The method of  claim 30 , wherein said metal nanoparticle comprises a gold nanoparticle. 
     
     
         38 . The method of  claim 30 , wherein said metal nanoparticle has a diameter of less than about 100 micrometers. 
     
     
         39 . The method of  claim 30 , wherein said linker comprises a sulfur. 
     
     
         40 . The method of  claim 30 , wherein said carbocyanine dye has a structure selected from the group consisting of: tricarbocyanine, pentacarbocyanine and heptacarbocyanine. 
     
     
         41 . A method of detecting and destroying cancer cells, comprising:
 introducing a composition into an organism suspected of having cancer cells;
 wherein said composition comprises a carbocyanine dye covalently attached to a metal nanoparticle via a linker bound to a nitrogen of an indole moiety of said carbocyanine dye; 
 wherein said linker comprises a polyethylene group; and 
 wherein said composition selectively binds to said cancer cells; 
   shining a near infrared light on a region suspected of having said cancer cells;   detecting a fluorescence from said composition to locate said cancer cells; and   targeting a beam of radio frequency energy at said region to induce hyperthermia in said cancer cells.   
     
     
         42 . The method of  claim 41 , wherein said fluorescence is emitted by said carbocyanine dye. 
     
     
         43 . The method of  claim 41 , wherein said composition does not bind to healthy cells. 
     
     
         44 . The method of  claim 41 , wherein said carbocyanine dye absorbs light having a wavelength ranging from between about 680 nanometers to about 1200 nanometers. 
     
     
         45 . The method of  claim 41 , wherein said carbocyanine dye comprises a heptamethine cyanine dye. 
     
     
         46 . The method of  claim 45 , wherein said heptamethine cyanine dye absorbs light having a wavelength ranging from between about 780 nanometers to about 1100 nanometers. 
     
     
         47 . The method of  claim 41 , wherein said induction of hyperthermia is facilitated by said metal nanoparticle. 
     
     
         48 . The method of  claim 41 , wherein said metal nanoparticle comprises a gold nanoparticle. 
     
     
         49 . The method of  claim 41 , wherein said metal nanoparticle has a diameter of less than about 100 micrometers. 
     
     
         50 . The method of  claim 41 , wherein said linker comprises a sulfur. 
     
     
         51 . The method of  claim 41 , wherein said carbocyanine dye has a structure selected from the group consisting of: tricarbocyanine, pentacarbocyanine and heptacarbocyanine.