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Development of photosensitizers effective for cancer therapy by laser light

开发对激光癌症治疗有效的光敏剂

基本信息

批准号：
13554025
负责人：
INOUE Hidenari
金额：
$ 3.14万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13554025/
关键词：
Chlorophyll Water-soluble chlorophylls cationic chlorophyll chlorin photosensitizer DNA cancer therapy PDT がん

项目摘要

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.

叶绿素类化合物不仅是光合作用系统中光捕获中心的模型，也是癌症光动力治疗的光敏剂，受到人们的广泛关注。其中一些化合物作为光动力学治疗的光敏剂非常有效，因为它们与癌细胞中的DNA有很强的相互作用，并且在可见光照射下DNA发生光振荡。本研究开发了三种有希望作为癌症治疗光敏剂的水溶性叶绿素衍生物。通过电子吸收光谱、圆二色谱和DNA熔融温度的测定，研究了它们与DNA茶的相互作用。用琼脂糖凝胶电泳法研究了在叶绿素衍生物存在下DNA的光振荡。第一类阴离子叶绿素衍生物，如金属绿素e_6钠，在生理条件下与DNA相互作用，在可见光照射下引起质粒DNA断裂。第二类两性(氯素e_6)-糖胺偶联物与小牛胸腺DNA发生强烈的相互作用，引起质粒DNA的光振荡。第三类阳离子氯e_6衍生物插入DNA碱基对之间，由于形成单线态氧而诱导了有效的质粒DNA光致发光。所有的水溶性叶绿素衍生物的DNA结合和DNA光致发光都受到中心金属离子种类和大环氯环外围基团的影响。综上所述，本文合成的所有叶绿素类化合物在可见光照射下都能与双螺旋DNA相互作用，导致质粒DNA断裂。