Study of Photosensitizers for Effective Photodynamic Theraphy of Cancer

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Plasmid DNA has been efficiently photocleaved by pheophorbides (Phdes) a and b. Irrespective of the presence of oxygen, Phde b has photocleaved DNA more effectively than phde a.Photocleavage efficiency of Phde b in the presence of oxygen is higher than in the absence of oxygen. In contrast, the efficiency of Phde a in the presence of oxygen is lower than in the absence of oxygen.The quantum yields of singlet oxygen (^1O_2) production are obtained by using a very reactive ^1O_2 acceptor, tetramethylene or furluryl alcohol. Singlet oxygen production sensitized by Phdes a or b can not be observed in the aqueous media (Tris-HC1/EDTA butter, pH7.4-7.9 or phosphate butter, pH7.4). Thus, the increase of photocleavege by Phde b in the presence of oxygen is not due to the formation of singlet oxygen. In organic solvents, however, Phde a shows the high quantum yields for ^1O_2 production : 0.61 in methanol and 0.85 in toluene.Fluorescence microscopic observation has shown a rapid incorporation of pheophorbide a into nuclei, mitochondria and lysosome of human oral mucosa cells. A long time irradiation produces a color change of folrescence from red to orange, indicating that some photochemical reactions take place in the above orangelle.Uptake of Phde a by tumor cells is also observed, although it is not clear where Phde a is located in the cells.These results suggest that Phde a is likely to scissors DNA,probably in mitochondria, in photodynamic therapy, and higher therapeutic effect can be expected by use of Phde b in place of Phde a.