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A Zero Cross-Talk Ratiometric Two-Photon Probe for Imaging of Acid pH in Living Cells and Tissues and Early Detection of Tumor in Mouse Model
Analytical Chemistry ( IF 6.7 ) Pub Date : 2018-07-02 00:00:00 , DOI: 10.1021/acs.analchem.8b00520
Di Xu 1 , Yinhui Li 2 , Chung-Yan Poon 1 , Hei-Nga Chan 1 , Hung-Wing Li 1 , Man Shing Wong 1
Affiliation  

Acid–base disorders disrupt proper cellular functions, which are associated with diverse diseases. Development of highly sensitive pH probes being capable of detecting and monitoring the minor changes of pH environment in living systems is of considerable interest to diagnose disease as well as investigate biochemical processes in vivo. We report herein two novel high-resolution ratiometric two-photon (TP) fluorescent probes, namely, PSIOH and PSIBOH derived from carbazole–oxazolidine π-conjugated system for effective sensing and monitoring acid pH in a biological system. Remarkably, PSIOH exhibited the largest emission shift of ∼169 nm from 435 to 604 nm upon pH changing from basic to acidic with an ideal pKa value of 6.6 within a linear pH variation range of 6.2–7.0, which is highly desirable for high-resolution tracking and imaging the minor fluctuation of pH in live cells and tissues. PSIOH also exhibits high pH sensitivity, excellent photostability, and reversibility as well as low cytotoxicity. More importantly, this probe was successfully applied to (i) sense and visualize the pH alteration in HeLa cells caused by various types of exogenous stimulation and (ii) detect and differentiate cancer and tumors in liver tissues and a mouse model, realizing its practical in vitro and in vivo applications.

中文翻译:

零交叉对话比率双光子探针,用于活细胞和组织中酸性pH成像并在小鼠模型中早期检测肿瘤

酸碱失调会破坏正常的细胞功能,这与多种疾病有关。能够检测和监测生命系统中pH环境的细微变化的高灵敏度pH探针对于诊断疾病以及研究体内生化过程具有重大意义。我们在此报告了两种新颖的高分辨率比例式双光子(TP)荧光探针,即源自咔唑-恶唑烷π共轭系统的PSIOH和PSIBOH,可有效检测和监测生物系统中的酸pH。值得注意的是,在pH从碱性变为酸性且理想的p K a时,PSIOH在435至604 nm处显示出最大的发射位移,从435 nm移至604 nm。pH值在6.2–7.0的线性范围内,为6.6,这对于高分辨率跟踪和成像活细胞和组织中pH的微小波动非常有用。PSIOH还具有高pH敏感性,出色的光稳定性和可逆性以及低细胞毒性。更重要的是,该探针已成功应用于(i)感知和可视化由各种类型的外源性刺激引起的HeLa细胞中的pH改变,以及(ii)检测和区分肝组织和小鼠模型中的癌症和肿瘤,实现了其实用性。体外体内应用。
更新日期:2018-07-02
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