Photophysical, photochemical, and tumor-selectivity properties of bromine derivatives of rhodamine-123
Photophysical, photochemical, and tumor-selectivity properties of bromine derivatives of rhodamine-123
复制标题
DOI：
10.1562/2005-08-05-ra-639
复制
发表时间：
2005-11-01
影响因子：
3.3
通讯作者：
Indig, GL
中科院分区：
文献类型：
--
作者：
Lacerda, SHD;Abraham, B;Indig, GL
发展线粒体靶向作为肿瘤疾病的化疗和光化疗的新型治疗策略的概念基础在于观察到增强的线粒体膜电位是常见的肿瘤细胞表型。这种策略的潜力是突出的事实，即与已知定位在通电的细胞线粒体中的一些阳离子染料相关的毒性作用在肿瘤细胞中比在正常细胞中明显得多。在这里，我们评估了四溴衍生物的罗丹明-123对人类子宫肉瘤（MES-SA）和绿色猴肾（CV-1）细胞的光毒性，并比较与这些染料与两个模型线粒体三芳基甲烷（结晶紫和乙基紫）相关的肿瘤细胞的选择性的程度。发现对肿瘤细胞的选择性光毒性高度依赖于阳离子光敏剂的亲脂/亲水特性。我们的实验数据表明，当候选药物福尔斯的辛-1-醇/水分配系数落在原型的线粒体特异性染料罗丹明-123的约两个数量级内时，在肿瘤疾病的（光）化疗中线粒体靶向成功的概率较高。
The conceptual basis for the development of mitochondrial targeting as a novel therapeutic strategy for both chemotherapy and photochemotherapy of neoplastic diseases rests on the observation that enhanced mitochondrial membrane potential is a common tumor cell phenotype. The potential of this strategy is highlighted by the fact that the toxic effects associated with a number of cationic dyes known to localize in energized cell mitochondria are much more pronounced in tumor cells than in normal cells. Here we evaluate the phototoxic properties of four bromine derivatives of rhodamine-123 toward human uterine sarcoma (MES-SA) and green monkey kidney (CV-1) cells and compare the degrees of tumor cell selectivity associated with these dyes with those associated with two model mitochondrial triarylmethanes (crystal violet and ethyl violet). Selective phototoxicity toward tumor cells was found to be highly dependent upon the lipophilic/hydrophilic character of the cationic photosensitizer. Our experimental data have indicated that the probability of success of mitochondrial targeting in (photo)chemotherapy of neoplastic diseases is higher when the octan-1-ol/water partition coefficient of the drug candidate falls within approximately two orders of magnitude from that of the prototypical mitochondria-specific dye rhodamine-123.