Selective photosensitization of mitochondria in HeLa cells by cationic Zn(II) phthalocyanines with lipophilic side-chains
Selective photosensitization of mitochondria in HeLa cells by cationic Zn(II) phthalocyanines with lipophilic side-chains
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DOI：
10.1016/s1011-1344(96)07416-7
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发表时间：
1997-02-01
影响因子：
5.4
通讯作者：
Zimmermann, HW
中科院分区：
文献类型：
--
作者：
Dummin, H;Cernay, T;Zimmermann, HW
为了优化线粒体的光敏作用，我们制备了具有亲脂性侧链的新型阳离子酞菁锌（2，9，16，23-四（三甲基铵基）酞菁锌（II）四甲基硫酸盐（ZnPcA 1）和2，9，16，23-四（三甲基铵基）酞菁锌（己基二甲基铵基）酞菁锌（II）四甲基硫酸盐（ZnPcA 6）），并将它们与已知的阳离子亲脂性敏化剂2，9，16进行比较，23-四[2-（三甲基铵基）乙氧基]酞菁锌（II）四碘化物（ZnPcE 1）和2，9，16，23-四[2-（己基二甲基铵基）乙氧基]酞菁锌（II）四溴化物（ZnPcE 6）和阴离子亲水性磺化敏化剂ZnPcS。研究了ZnPcA_1的吸收光谱、荧光光谱、荧光量子产率、辛醇/水分配系数、ZnPcA_1在水中的二聚反应以及单线态氧的光敏化生成。此外，研究了酞菁类化合物对HeLa细胞的光毒性和细胞毒作用，它们对增殖速率的光动力作用以及辐射对呼吸活性的影响，并与孵育和辐射的HeLa细胞的超微结构的电子显微镜和荧光显微镜观察进行了比较。从我们的实验中，我们得出结论，阳离子亲脂性增感剂，如ZnPcA 6等，特别是聚集在线粒体内膜中。因此，它们可用于线粒体的选择性光敏化。在照射孵育的HeLa细胞时，嵴受到影响并最终完全破坏。呼吸停止，能量代谢中断。实验结果表明，敏化剂的光毒性效应顺序为：ZnPcA_6> ZnPcA_1> ZnPcE_6> ZnPcE_1> ZnPcS。阳离子亲脂性ZnPcA 6具有最强的光毒性活性。它在非常低的致敏剂浓度和短的照射时间内对孵育起作用。暗毒性完全可以忽略。光毒性活性遵循II型机制。(C)1997年Elsevier Science S.A.
In order to optimize the photosensitization of mitochondria, we prepared the new cationic zinc(II) phthalocyanines with lipophilic side-chains (2,9,16,23-tetrakis(trimethylammonio)zinc(II)phthalocyanine tetramethylsulphate (ZnPcA1) and 2,9,16,23-tetrakis(hexyldimethylammonio)zinc(II)phthalocyanine tetramethylsulphate (ZnPcA6)) and compared them with the known cationic lipophilic sensitizers 2,9,16,23-tetrakis[2-(trimethylammonio)ethoxy]zinc(II)phthalocyanine tetraiodide (ZnPcE1) and 2,9,16,23-tetrakis[2-(hexyldimethylammonio)ethoxy]zinc(II)phthalocyanine tetrabromide (ZnPcE6) and the anionic hydrophilic sulphonated sensitizer ZnPcS. The absorption and fluorescence spectra, fluorescence quantum yields, partition coefficients P-o/w between octanol and water, dimerization of ZnPcA1 in water and photosensitized generation of singlet oxygen were examined. Moreover, the phototoxic and cytotoxic effects of the phthalocyanines on HeLa cells, their photodynamic action on the proliferation rate and the influence of irradiation on the respiratory activity were studied and compared with electron and fluorescence microscopic observations of the ultrastructure of incubated and irradiated HeLa cells. From our experiments, we conclude that cationic lipophilic sensitizers, such as ZnPcA6, etc., specifically accumulate in the inner mitochondrial membranes. Therefore they can be used for the selective photosensitization of mitochondria. On irradiation of the incubated HeLa cells, the cristae are affected and finally completely destroyed. The respiration stops and the energy metabolism breaks down. Our experiments indicate that the phototoxic efficacy of the sensitizers decreases in the following order: ZnPcA6 > ZnPcA1 > ZnPcE6 > ZnPcE1 > ZnPcS. The cationic lipophilic ZnPcA6 has the strongest phototoxic activity. It acts on incubation at very low sensitizer concentrations and short irradiation periods. The dark toxicity is completely negligible. The phototoxic activity follows the type II mechanism. (C) 1997 Elsevier Science S.A.