Composition and method for causing photodynamic damage to target cells

Abstract

The present invention is directed to a composition for causing photodynamic damage to target cells comprising a photosensitizer, a photosensitizer carrier component, a component which enables target cell recognition and transport of the photosensitizer toward the interior of the target cell by specific receptor-mediated endocytosis, and a component capable of effective targeted transport of the photosensitizer within the target cells. The invention is also related to a method for causing photodynamic damage to target cells comprising the steps of: adding the composition to the cells; keeping the cells at a temperature of normal vital activity of cells with the composition for causing photodynamic damage to the target cells, said composition comprising the above-mentioned components; and exposure of the cells to light.

What is claimed is:  
     
         1 . A composition for causing photodynamic damage to target cells, comprising: 
 a photosensitizer;    a carrier for the photosensitizer;    an endosomolytic component;    a first component which enables target cell recognition and transport of the photosensitizer toward the interior of the target cell by specific receptor-mediated endocytosis; and    a karyophilic moiety for targeted transport of the photosensitizer to the nucleus of the target cells;    wherein the carrier is bound to the first component and/or to the karyophilic moiety.    
     
     
         2 . The composition according to  claim 1 , wherein said endosomolytic component is adenovirus.  
     
     
         3 . The composition according to  claim 2 , wherein said adenovirus is human adenovirus, type 5, strain d1-312.  
     
     
         4 . The composition according to  claim 1 , wherein said photosensitizer carrier is a polymer.  
     
     
         5 . The composition according to  claim 4 , wherein said polymer is a protein.  
     
     
         6 . The composition according to  claim 5 , wherein said protein is bovine serum albumin.  
     
     
         7 . The composition according to  claim 5 , wherein said protein is a recombinant polypeptide.  
     
     
         8 . The composition according to  claim 7 , wherein said recombinant polypeptide is a bacterial β-galactosidase fused with said karyophylic moiety, said moiety being a karyophylic sequence of the SV40 large T-antigen.  
     
     
         9 . The composition according to  claim 1 , wherein said first component which enables target cell recognition and transport of the photosensitizer toward the interior of the target cell by specific receptor-mediated endocytosis is an internalizable ligand.  
     
     
         10 . The composition according to  claim 9 , wherein said internalizable ligand is a peptide hormone.  
     
     
         11 . The composition according to  claim 10 , wherin said peptide hormone is insulin.  
     
     
         12 . The composition according to  claim 1 , wherein said photosensitizer is chlorin e 6 .  
     
     
         13 . A method for causing photodynamic damage to target cells, comprising the steps of: 
 contacting the target cells with a composition for causing photodynamic damage to target cells, said composition comprising: 
 a photosensitizer;  
 a carrier for the photosensitizer;  
 an endosomolytic component;  
 a first component which enables target cell recognition and transport of the photosensitizer toward the interior of the target cell by specific receptor-mediated endocytosis; and  
 a karyophilic moiety for targeted transport of the photosensitizer to the nucleus of the target cells;  
 wherein the carrier is bound to the first component and/or to the karyophilic moiety so as to produce a population of treated cells by targeted transport of said photosensitizer into the target cells;  
   said method further comprising the steps of keeping the population of treated cells at a temperature of normal vital activity of cells for a period of time; and    exposing the population of treated cells to light, thereby causing photodynamic damage to the target cells.    
     
     
         14 . The method according to  claim 13 , wherein said composition for causing photodynamic damage is directed to the nucleus of the target cells by targeted transport.  
     
     
         15 . The method according to  claim 13 , wherein said composition for causing photodynamic damage is released from endocytotic compartments.