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Study of Photosensitizers for Effective Photodynamic Theraphy of Cancer

有效光动力治疗癌症的光敏剂研究

基本信息

批准号：
04555193
负责人：
KOMIYAMA Makoto
金额：
$ 3.2万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

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.

质粒DNA已被脱镁叶绿酸（Phdes）a和B有效地光切割。无论氧的存在与否，Phde B比Phde a更有效地光切割DNA。Phde B在氧存在下的光切割效率高于在无氧存在下的光切割效率。用四氢呋喃或呋喃甲醇作为^1O_2的活性受体，得到了单重态氧（^1O_2）的量子产率。Phdes a或B敏化的单线态氧产生在水介质（Tris-HCl/EDTA黄油，pH 7.4 -7.9或磷酸盐黄油，pH 7.4）中不能观察到。因此，在氧存在下Phde B的光裂解的增加不是由于单线态氧的形成。在有机溶剂中，Phde a产生^1O_2的量子产率很高，在甲醇中为0.61，在甲苯中为0.85.荧光显微镜观察显示脱镁叶绿酸a可迅速掺入人口腔粘膜细胞的细胞核、线粒体和溶酶体中.长时间照射后，荧光由红色变为橙子，表明在上述橙色区域发生了某些光化学反应，还观察到Phde a被肿瘤细胞摄取，但尚不清楚Phde a在细胞中的位置，这些结果表明Phde a在光动力疗法中可能剪切DNA，可能是在线粒体中，用Phde B代替Phde a可望获得更高的疗效。