A novel nitro-substituted benzothiadiazole as fluorescent probe for tumor cells under hypoxic condition
A novel nitro-substituted benzothiadiazole as fluorescent probe for tumor cells under hypoxic condition
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一种新型硝基取代苯并噻二唑作为缺氧条件下肿瘤细胞的荧光探针
DOI：
10.1016/j.bmc.2013.10.019
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发表时间：
2013-12-15
影响因子：
3.5
通讯作者：
Jiang, Qing
中科院分区：
文献类型：
--
作者：
Jiang, Qian;Zhang, Zhanyuan;Jiang, Qing
大多数实体瘤细胞都是缺氧的，难以追踪和测量。本文合成了一种新的化合物4,7-双(4-十二烷基噻吩-2-基)-5,6-二硝基苯并[c][1,2,5]噻二唑(BTTD-NO2),专门用于标记缺氧细胞。 MTT法显示BTTD-NO2对MG63细胞无细胞毒性。当MG63细胞与BTTD-NO2在低氧条件下培养24小时时，在细胞质中观察到强烈的红色荧光分布。流式细胞术结果显示，在缺氧条件下，65%的MG63细胞被强烈的红色荧光标记，而在有氧条件下，只有2.4%的MG63细胞被标记为强红色荧光。此外，实时RT-PCR证明BTTD-NO2可以刺激细胞内硝基还原酶基因的高表达，从而提高BTTD-NO2向BTTD-NH2的转化率。证明BTTD-NO2的荧光被其两个硝基猝灭，但在肿瘤细胞缺氧条件下，其硝基被还原为氨基后，细胞质中可发出强烈的红色荧光。这些结果表明 BTTD-NO2 有潜力作为肿瘤检测的优质荧光探针。 (C) 2013 Elsevier Ltd. 保留所有权利。
Most of solid tumor cells are hypoxic and hard to trace and measure. A new compound, 4,7-bis(4-dodecylthiophen-2-yl)-5,6-dinitrobenzo[c][1,2,5]thiadiazole (BTTD-NO2), was synthesized for labeling the hypoxic cells specially in this paper. BTTD-NO2 showed no cytotoxicity to MG63 cells by MTT method. When MG63 cells were cultured with BTTD-NO2 under hypoxic condition for 24 h, strong red fluorescence distribution in cytoplasm was observed. Flow cytometry results showed that 65% of MG63 cells were labeled with strong red fluorescence in hypoxic condition while only 2.4% in oxic condition. Furthermore, Real time RT-PCR proved that BTTD-NO2 could stimulate high gene expression of the nitroreductase in the cells which could improve the conversion rate of BTTD-NO2 to BTTD-NH2 in turn. It proved that the fluorescence of BTTD-NO2 was quenched by its two nitro groups, however, strong red fluorescence could emit in the cytoplasm after the reduction of its nitro groups to amino groups in the tumor cells under hypoxic condition. These results suggested that BTTD-NO2 had the potential as a superior fluorescent probe for tumor detection. (C) 2013 Elsevier Ltd. All rights reserved.