Development of photosensitizers effective for cancer therapy by laser light

叶绿素衍生物不仅作为光合系统中光收集中心的模型，而且作为光动力治疗癌症的光敏剂受到广泛关注。其中一些与癌细胞中的DNA有很强的相互作用，在可见区激光照射下DNA发生光分裂，因此作为光动力治疗的光敏剂是非常有效的。目前的研究开发了三种水溶性叶绿素衍生物，它们作为光敏剂在癌症治疗中具有很大的前景。通过电子吸收和圆二色光谱以及DNA熔化温度的测量研究了它们与DNA茶的相互作用。用琼脂糖凝胶电泳研究了叶绿素衍生物存在下DNA的光分裂。第一类阴离子叶绿素衍生物如金属氯钠e_6在生理条件下与DNA相互作用，在可见光照射下导致质粒DNA断裂。第二种两性（氯e_6）-糖酰胺偶联物与小牛胸腺DNA强烈相互作用，引起质粒DNA的光分裂。第三种阳离子氯离子e_6衍生物插入DNA碱基对之间，通过单线态氧的形成诱导质粒DNA发生有效的光分裂。所有水溶性叶绿素衍生物的DNA结合和DNA光导作用都受到中心金属离子种类和大环氯环外周基团的影响。综上所述，本文所合成的叶绿素衍生物均与双螺旋DNA相互作用，在可见光照射下引起质粒DNA的断裂。

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.