Sugar-dependent aggregation of glycoconjugated chlorins and its effect on photocytotoxicity in HeLa cells
Sugar-dependent aggregation of glycoconjugated chlorins and its effect on photocytotoxicity in HeLa cells
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DOI：
10.1016/j.jphotobiol.2006.01.011
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发表时间：
2006-07-03
影响因子：
5.4
通讯作者：
Yano, Shigenobu
中科院分区：
文献类型：
--
作者：
Hirohara, Shiho;Obata, Makoto;Yano, Shigenobu
为了探讨糖结合氯对光细胞毒性的影响，我们研究了四种糖结合氯在细胞质等水介质中的光化学性质以及在HeLa细胞中光细胞毒性的浓度依赖关系。在磷酸盐缓冲溶液中，5，10，15，20-tetrakis[3-(beta-D-glucopyranosyloxy)phenyl]chlorin(m-1a)和5，10，15，20-tetrakis[3-(beta-D-galactopyranosyloxy)phenyl]chlorin(m-1b)，即具有己糖基的氯离子的荧光强度比5，10，15，20-tetrakis[3-(beta-D-xylopyranosyloxy)phenyl]chlorin(m-1c)和5，10，15，20-tetrakis[3-(beta-Darabinopyranosyloxy)phenyl]chlorin(m-1d)，即具有戊糖基的氯离子的荧光强度大约2倍，由于糖依赖的聚集行为的差异。M-1a对HeLa细胞的光细胞毒作用最强，抑制率为82%。高于m-1b、m-1c、m-1d和四苯基卟啉四磺酸。除m-1b外，糖结合的氯素弥漫分布于细胞质中。在四种光敏剂中，m-1a在共聚焦荧光图像中显示出最高的强度，这与体外光细胞毒实验结果一致。对于m-1c，在0.2-0.04M的药物浓度范围内没有发现光细胞毒性，因此糖依赖的聚集不是m-1c意外缺乏疗效的主要原因，而m-1c被HeLa细胞有效地摄取。对于糖结合的绿素，这些结果表明，糖部分的生物学方面比化学方面起到了更关键的作用。(C)2006爱思唯尔B.V.保留所有权利。
in order to explore the influence of the sugar moieties of glycoconjugated chlorins on the photocytotoxicity, we studied the photochemical properties of four glycoconjugated chlorins in aqueous media such as cytoplasm and the concentration dependence of photocytotoxicity in HeLa cells. In phosphate-buffered saline, the fluorescence intensities of 5,10,15,20-tetrakis[3-(beta-D-glucopyranosyloxy)phenyl]chlorin (m-1a) and 5,10,15,20-tetrakis[3-(beta-D-galactopyranosyloxy)phenyl]chlorin (m-1b), i.e., chlorins having hexose groups, were about 2-fold greater than those of 5,10,15,20-tetrakis[3-(beta-D-xylopyranosyloxy)phenyl]chlorin (m-1c) and 5,10,15,20-tetrakis[3-(beta-Darabinopyranosyloxy)phenyl]chlorin (m-1d), i.e., chlorins having pentose groups, owing to a sugar-dependent difference of aggregation behavior. While no cytotoxicity was found in the dark, the highest photocytotoxicity was shown by m-la (82% inhibition) in HeLa cells. This was higher than those of m-1b, m-1c, m-1d and tetraphenylporphyrin tetrasulfonic acid. The glycoconjugated chlorins except for m-1b appeared to be distributed diffusely throughout the cytoplasm. Among the four photosensitizers, m-la showed the highest intensity in confocal fluorescence images, in agreement with the in vitro photocytotoxicity results. For m-1c, no photocytotoxicity was found at drug concentrations from 0.2 to 0.04 M. Hence, sugar-dependent aggregation is not the major reason for the unexpected lack of efficacy of m-1c, which is uptaken efficiently by HeLa cells. For the glycoconjugated chlorins, these results suggest the biological aspects of sugar moiety play much crucial role rather than chemical aspects. (c) 2006 Elsevier B.V. All rights reserved.