Dye-azide compounds for dual phototherapy

Abstract

The present invention discloses dye-azide derivatives and their bioconjugates for dual phototherapy of tumors and other lesions. The compounds of the present invention may contain either a mixture of Type 1 and Type 2 agents or a single entity that integrates both units in the same molecules. The compounds are designed to produce both Type 1 and Type 2 phototherapeutic effect at once using dual wavelength light source that will produce singlet oxygen and nitrene at the lesion of interest.

What is claimed is:  
     
         1 . A compound comprising organic azides having the general formula  
       E----L----DYE----X-----N 3    wherein DYE is an aromatic or a heteroaromatic radical derived from the group consisting of cyanines, indocyanines, phthalocyanines, rhodamines, phenoxazines, phenothiazines, phenoselenazines, fluoresceins, porphyrins, benzoporphyrins, squaraines, corrins, croconiums, azo dyes, methine dyes, and indolenium dyes; E is a hydrogen atom or is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, steroid receptor binding molecules, and carbohydrate receptor binding molecules; L is selected from the group consisting of —(CH 2 ) a —, —(CH 2 ) b CONR 1 —, —N(R 2 )CO CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —OCONH—, —OCO 2 —, —HNCONH—, —HNCSNH—, HNNHCO—, —OSO 2 —, —NR 3 (CH 2 ) e CONR 4 —, —CONR 5 (CH 2 ) f NR 6 CO—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —HNCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—; R 1  to R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, —OH, C1-C10 polyhydroxyalkyl, C1-C10 alkoxyl, C1-C10 alkoxyalkyl, —SO 3 H, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C5-C10 aryl, and C1-C10 polyhydroxyalkyl; and a to l independently range from 0 to 10.    
     
     
         2 . The compound of  claim 1  wherein DYE is an aromatic or a heteroaromatic radical derived from cyanines; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—. R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         3 . The compound of  claim 1  wherein DYE is an aromatic or a heteroaromatic radical derived from phthalocyanines; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         4 . The compound of  claim 1  wherein DYE is an aromatic or a heteroaromatic radical derived from rhodamines; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         5 . The compound of  claim 1  wherein DYE is an aromatic or a heteroaromatic radical derived from porphyrins; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         6 . The compound of  claim 1  wherein DYE is an aromatic or heteroaromatic radical derived from benzoporphyrins; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         7 . The compound of  claim 1  wherein DYE is an aromatic or heteroaromatic radical derived from corrins; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         8 . The compound of  claim 1  wherein DYE is an aromatic or heteroaromatic radical derived from phenothiazines; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         9 . The compound of  claim 1  wherein DYE is an aromatic or heteroaromatic radical derived from hypocrellins; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         10 . The compound of  claim 1  wherein DYE is an aromatic or heteroaromatic radical derived from indolenium dyes; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         11 . The compound of  claim 1  wherein E is associated with a biomolecule selected from the group consisting of hormones, amino acids, peptides, peptidomimetics, proteins, nucleosides, nucleotides, nucleic acids, enzymes, carbohydrates, glycomimetics, lipids, albumins, monoclonal antibodies, polyclonal antibodies, receptors, inclusion compounds, receptor binding molecules, polyaminoacids, polyols, polyamines, polyacids, oligonucleotides, aborols, dendrimers, and aptamers.  
     
     
         12 . A method of performing a phototherapeutic procedure which comprises the steps of: 
 (a) administering to a target tissue in an animal an effective amount of organic azide photosensitizer having the formula    E----L----DYE----X-----N 3      wherein DYE is an aromatic or a heteroaromatic radical derived from the group consisting of cyanines, indocyanines, phthalocyanines, rhodamines, phenoxazines, phenothiazines, phenoselenazines, fluoresceins, porphyrins, benzoporphyrins, squaraines, corrins, croconiums, azo dyes, methine dyes, and indolenium dyes; E is a hydrogen atom or is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, steroid receptor binding molecules, and carbohydrate receptor binding molecules; L is selected from the group consisting of —(CH 2 ) a —, —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —OCONH—, —OCO 2 —, —HNCONH—, —HNCSNH—, —HNNHCO—, —OSO 2 —, —NR 3 (CH 2 ) e CONR 4 —, —CONR 5 (CH 2 ) f NR 6 CO—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —HNCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—; R 1  to R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, —OH, C1-C10 polyhydroxyalkyl, C1-C10 alkoxyl, C1-C10 alkoxyalkyl, —SO 3 H, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C5-C10 aryl, and C1-C10 polyhydroxyalkyl; and a to l independently range from 0 to 10; and    (b) exposing said target tissues with the light of wavelength between 300 and 950 nm with sufficient power and fluence rate to cause necrosis or apoptosis of the said target tissue.    
     
     
         13 . The method of  claim 12  further comprising the step of allowing said photosensitizer to accumulate in said target tissue.  
     
     
         14 . The method of  claim 12 , wherein DYE is an aromatic or a heteroaromatic radical derived from cyanines; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9 , and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         15 . The method of  claim 12 , wherein DYE is an aromatic or a heteroaromatic radical derived from phthalocyanines; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         16 . The method of  claim 12 , wherein DYE is an aromatic or a heteroaromatic radical derived from rhodamines; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         17 . The method of  claim 12 , wherein DYE is an aromatic or a heteroaromatic radical derived from porphyrins; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         18 . The method of  claim 12 , wherein DYE is an aromatic or a heteroaromatic radical derived from benzoporphyrins; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         19 . The method of  claim 12 , wherein DYE is an aromatic or a heteroaromatic radical derived from corrins; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         20 . The method of  claim 12 , wherein DYE is an aromatic or a heteroaromatic radical derived from phenothiazines; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR9R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         21 . The method of  claim 12 , wherein DYE is an aromatic or a heteroaromatic radical derived from hypocrellins; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         22 . The method of  claim 12 , wherein DYE is an aromatic or a heteroaromatic radical derived from indolenium dyes; E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholesystekinin receptor binding molecules, and steroid receptor binding molecules; L is selected from the group consisting of —(CH 2 ) b CONR 1 —, —N(R 2 )CO(CH 2 ) c —, —OCO(CH 2 ) d —, —(CH 2 ) e CO 2 —, —HNCONH—, —HNCSNH—, and —NR 7 CO(CH 2 ) g CONR 8 —; X is either a single bond or is selected from the group consisting of —(CH 2 ) h —, —OCO—, —(CH 2 ) i CO—, and —(CH 2 ) j OCO—., R 1 , R 2 , R 7  and R 8  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 polyhydroxyalkyl, —(CH 2 ) k CO 2 H, and —(CH 2 ) l NR 9 R 10 ; R 9  and R 10  are independently selected from the group consisting of hydrogen, C1-C10 alkyl, and C1-C10 polyhydroxyalkyl; and b-e and g-j independently range from 0 to 6.  
     
     
         23 . The method of  claim 12  wherein E is associated with a biomolecule selected from the group consisting of hormones, amino acids, peptides, peptidomimetics, proteins, nucleosides, nucleotides, nucleic acids, enzymes, carbohydrates, glycomimetics, lipids, albumins, monoclonal antibodies, polyclonal antibodies, receptors, inclusion compounds, receptor binding molecules, polyaminoacids, polyols, polyamines, polyacids, oligonucleotides, aborols, dendrimers, and aptamers.  
     
     
         24 . The method of  claim 23  wherein the effective amount of the organic azide photosensitizer administered to the target tissue is in a range of about 0.1 mg/kg body weight to about 500 mg/kg body weight.  
     
     
         25 . The method of  claim 24  wherein the effective amount of the organic azide photosensitizer administered to the target tissue is in a range of about 0.5 mg/kg body weight to about 2 mg/kg body weight.  
     
     
         26 . The method of  claim 12  wherein the organic azide photosensitizer is parenterally administered to the target tissue in a formulation including the organic azide photosensitizer and materials selected from the group consisting of pharmaceutically acceptable buffers, emulsifiers, surfactants, and electrolytes.  
     
     
         27 . The method of  claim 26  wherein the formulation is parenterally administered to the target tissue in a concentration in a range of about 1 nM to about 0.5 M.  
     
     
         28 . The method of  claim 12  wherein the organic azide photosensitizer is enterally administered to the target tissue in a formulation including the organic azide photosensitizer and materials selected from the group consisting of buffers, surfactants, emulsifiers, and thixotropic agents.  
     
     
         29 . The method of  claim 12  wherein the organic azide photosensitizer is topically administered to the target tissue in a formulation including the organic azide photosensitizer and materials selected from the group consisting of liquid excipients and semisolid excipients.  
     
     
         30 . The method of  claim 12  wherein the organic azide photosensitizer is administered in a form selected from the group consisting of an aerosol spray, a cream, a gel, and a solution.  
     
     
         31 . A method of performing a phototherapeutic procedure which comprises the steps of: 
 (a) preparing a homogeneous photosensitizing mixture consisting of two or more Type 1 agents,    (b) administering said photosensitizing mixture to a target tissue in an animal; and    (c) exposing said target tissues with the light of wavelength between 300 and 950 nm with sufficient power and fluence rate to cause necrosis or apoptosis of the said target tissue.    
     
     
         32 . The method of  claim 31 , wherein said photosensitizing mixture comprises azides.  
     
     
         33 . The method of  claim 32 , further comprising the step of allowing said photosensitizing mixture to accumulate in said target tissue.  
     
     
         34 . A method of performing a phototherapeutic procedure which comprises the steps of: 
 (a) preparing a homogeneous photosensitizing mixture consisting of two or more Type 2 (PDT) agents,    (b) administering said photosensitizing mixture to a target tissue in an animal; and    (c) exposing said target tissues with the light of wavelength between 300 and 950 nm with sufficient power and fluence rate to cause necrosis or apoptosis of the said target tissue.    
     
     
         35 . The method of  claim 34 , wherein said photosensitizing mixture comprises phthalocyanines and porphyrins.  
     
     
         36 . The method of  claim 35 , further comprising the step of allowing said photosensitizing mixture to accumulate in said target tissue  
     
     
         37 . A method of performing a phototherapeutic procedure which comprises the steps of: 
 (a) preparing a heterogeneous photosensitizing mixture consisting of one or more Type 1 agents and one or more Type 2 agents,    (b) administering said photosensitizing mixture to a target tissue in an animal; and    (c) exposing said target tissues with the light of wavelength between 300 and 950 nm with sufficient power and fluence rate to cause necrosis or apoptosis of the said target tissue.    
     
     
         38 . The method of  claim 37 , wherein said photosensitizing mixture comprises azides, phthalocyanines and porphyrins.  
     
     
         39 . The method of  claim 38 , further comprising the step of allowing said photosensitizing mixture to accumulate in said target tissue.