Department of Gastroenterology , Ajou University School of Medicine , Suwon 443-721 , Korea.
Anal Chem. 2018 Jul 3;90(13):8058-8064. doi: 10.1021/acs.analchem.8b01114. Epub 2018 Jun 11.
Acidified extracellular pH (pHe) is directly related to various disorders such as tumor invasion and the resistance to drugs. In this study, we developed two-photon-excitable emission ratiometric probes (XBH1-3) for the in situ measurement of pHe. These probes, based on benzimidazole and polar solubilizing groups, exhibited a strong two-photon-induced fluorescence and sensitive blue-to-green emission color changes with p K values of 5.1-5.7. XBH1, containing a carboxylic acid, stained the extracellular region in neutral media; it entered the cell under acidic media, thereby allowing a precise measurement of the extra- and intra-cellular pH values in the acidified tissue. XBH2, containing the sulfonate peripheral unit, facilitated the monitoring of the pHe value only. Ratiometric two-photon microscopy imaging revealed that XBH1 can directly monitor the pH values both inside and outside the cells in colon cancer tissue; there is also the morphological aspect. This could be useful for cancer analyses and drug development.
酸化的细胞外 pH 值(pHe)与各种疾病直接相关,如肿瘤浸润和药物耐药性。在这项研究中,我们开发了两种用于 pHe 原位测量的双光子激发发射比率探针(XBH1-3)。这些基于苯并咪唑和极性增溶基团的探针具有很强的双光子诱导荧光和敏感的蓝-绿发射颜色变化,pK 值为 5.1-5.7。含有羧酸的 XBH1 在中性介质中染色细胞外区域;在酸性介质下进入细胞,从而可以精确测量酸化组织中的细胞内外 pH 值。含有磺酸盐外围单元的 XBH2 仅有助于监测 pHe 值。比率双光子显微镜成像显示,XBH1 可以直接监测结肠癌组织中细胞内外的 pH 值;还有形态方面。这对于癌症分析和药物开发可能很有用。