Development of photosensitizers effective for cancer therapy by laser light

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The chlorophyll derivatives have received much attention not only as a model of the light harvesting center in photosynthetic system but also as a photosensitizer of photodynamic therapy of cancer. In particular, some of them are very effective as photosensitizers of photodynamic therapy because of their strong interaction with DNA in cancer cells and photoscission of DNA under the irradiation of the laser light in the visible region. Three types of water-soluble chlorophyll derivatives of great promise as photosensitizers of cancer therapy have been developed in the present study. Their interaction with DNA teas been studied by electronic absorption and circular dichroism spectroscopy and by measurements of melting temperature of DNA. The photoscission of DNA in the presence of the chlorophyll derivatives has been examined by agarose gel electrophoresis. The first type of anionic chlorophyll derivative such as sodium metallochlorin e_6 interacts with DNA under the physiological conditions and causes a scission of plasmid DNA under the illumination of visible light. The second type of amphoteric (chlorin e_6)-sugaramide conjugate interacts strongly with calf thymus DNA to cause a photoscission of plasmid DNA. The third type of cationic chlorin e_6 derivative is intercalated between the DNA base pairs to induce an effective photoscission of plasmid DNA due to the formation of singlet oxygen. The DNA binding and DNA photoscission of all the water-soluble chlorophyll derivatives are influenced by the kind of central metal ions and the peripheral groups of the macrocyclic chlorin ring. In conclusion, it has been demonstrated that all the chlorophyll derivatives Here synthesized interact with the double-helix DNA to gives rise to the scission of plasmid DNA under the irradiation of visible light.