Photodynamic therapy using chemiluminescence and a ligand-photosensitiser conjugate

Abstract

A method for destroying harmful cells is provided, applicable in treating proliferative diseases. The cells are destroyed by a combined treatment with a chemiluminescent agent and with a ligand-photosensitizer conjugate. The chemiluminescent agent emits light on reacting with oxygen species present in situ, the conjugate binds to the cell through its ligand and is activated by the emitted light, thereby destroying the cell. The method is demonstrated on a conjugate of transferrin-hematoporphyrin, which destroys cancerous cells in the presence of luminol.

1 . A pharmaceutical composition comprising a chemiluminescent agent, wherein said agent activates in situ a ligand-toxin conjugate. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein said ligand-toxin conjugate comprises a photosensitizer. 
     
     
         3 . The pharmaceutical composition according to  claim 2 , wherein said photosensitizer comprises hematoporphyrin. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein said chemiluminescent agent is selected from the group consisting of luminol, a luminol derivative, isoluminol and lucigenin. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein said chemiluminescent agent is coupled to said ligand-toxin conjugate. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein said ligand-toxin conjugate is accumulated in intracellular vesicles in situ. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein said ligand-toxin conjugate and said chemiluminescent agent act in synergy in destroying target cells in situ. 
     
     
         8 . A pharmaceutical composition comprising a ligand-toxin conjugate, wherein said ligand is a peptide, said toxin is a photosensitizer, and wherein said photosensitizer is activated in situ by a chemiluminescent agent. 
     
     
         9 . The pharmaceutical composition according to  claim 8 , wherein said peptide is recognized by a receptor on the surface of target cells present in situ. 
     
     
         10 . The pharmaceutical composition according to  claim 9 , wherein said peptide is transferrin. 
     
     
         11 . The pharmaceutical composition according to  claim 8 , wherein said photosensitizer comprises hematoporphyrin. 
     
     
         12 . The pharmaceutical composition according to  claim 8 , wherein said ligand-toxin conjugate comprises transferrin and hematoporphyrin being linked to the transferrin. 
     
     
         13 . The pharmaceutical composition according to  claim 8 , wherein said chemiluminescent agent is selected from the group consisting of luminol, a luminol derivative, isoluminol and lucigenin. 
     
     
         14 . The pharmaceutical composition according to  claim 8 , wherein said chemiluminescent agent is coupled to said ligand-toxin conjugate. 
     
     
         15 . The pharmaceutical composition according to  claim 8 , wherein said ligand-toxin conjugate is capable of accumulating in intracellular vesicles in situ. 
     
     
         16 . The pharmaceutical composition according to  claim 8 , wherein said ligand-toxin conjugate and said chemiluminescent agent act in synergy in destroying target cells in situ. 
     
     
         17 . A method for selectively destroying target cells, the method comprising:
 (i) contacting the target cells with a ligand-toxin conjugate which comprises a photosensitizer and a transport ligand linked to the photosensitizer; and   (ii) exposing the target cells to a chemiluminescent agent which reacts with an oxygen species present in situ and produces chemiluminescent light, thereby causing direct damage to the cellular components of said target cells.   
     
     
         18 . A method according to  claim 17 , wherein said ligand in said ligand-toxin conjugate comprises a peptide. 
     
     
         19 . A method according to  claim 18 , wherein said peptide is recognized by a receptor on the surface of the target cells. 
     
     
         20 . A method according to  claim 18 , wherein said peptide is transferrin. 
     
     
         21 . A method according to  claim 17 , wherein said photosensitizer comprises hematoporphyrin. 
     
     
         22 . A method according to  claim 17 , wherein said ligand-toxin conjugate comprises transferrin and hematoporphyrin being linked to the transferrin. 
     
     
         23 . A method according to  claim 17 , wherein said chemiluminescent agent is selected from the group consisting of luminol, a luminol derivative, isoluminol and lucigenin. 
     
     
         24 . A method according to  claim 22 , wherein said chemiluminescent agent is selected from the group consisting of luminol, a luminol derivative, isoluminol and lucigenin. 
     
     
         25 . A method according to  claim 17 , wherein said chemiluminescent agent is coupled to said ligand-toxin conjugate. 
     
     
         26 . A method according to  claim 17 , wherein said ligand-toxin conjugate is capable of accumulating in intracellular vesicles. 
     
     
         27 . A method according to  claim 17 , wherein said ligand-toxin conjugate and said chemiluminescent agent act in synergy in destroying the target cells. 
     
     
         28 . A method for selectively destroying target cells, the method comprising:
 (i) contacting the target cells with a ligand-toxin conjugate which comprises a hematoporphyrin photosensitizer and a transferrin transport ligand linked to the photosensitizer; and   (ii) exposing the target cells to a chemiluminescent agent which reacts with an oxygen species present in situ and produces chemiluminescent light, said chemiluminescent agent comprising a luminol or a luminol derivative, thereby causing direct damage to the cellular components of said target cells.   
     
     
         29 . A method according to  claim 28 , wherein said chemiluminescent agent is coupled to said ligand-toxin conjugate.