A highly selective ratiometric molecular probe for imaging peroxynitrite during drug-induced acute liver injury,Journal of Materials Chemistry B

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A highly selective ratiometric molecular probe for imaging peroxynitrite during drug-induced acute liver injury
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2021-08-19 , DOI: 10.1039/d1tb01534f
Xiangyang Gong ₁ , Dan Cheng _{1,

2} , Wei Li ₁ , Yang Shen ₁ , Rong Peng ₁ , Ling Shi ₁ , Longwei He ₃ , Lin Yuan ₁

Affiliation

Drug-induced acute liver injury (DIALI) is a common liver disease, affecting a number of people worldwide with increasing morbidity each year. Thus, it is vital to develop new tools for intervention and diagnosis. Peroxynitrite (ONOO⁻), a highly reactive species, plays an important role in the DIALI process. Thus, in situ molecular imaging of endogenous ONOO⁻ levels is considerably significant for detecting ONOO⁻. In this work, we present two destroyed-type ratiometric fluorescent probes, AHC and AHMC, for ONOO⁻ detection by using a molecular hybridization strategy. The probe AHMC was developed by introducing the ester structure to AHC directly to enhance its membrane penetrability for living cell imaging. Probe AHC exhibited good analytical performance toward ONOO⁻ compared to other reactive species, with a low detection limit (≈1.8 nM) and a strong ratiometric fluorescence response (134-fold). In cell imaging experiments, AHMC showed outstanding selectivity, favourable biocompatibility and mitochondria-targeting ability, which not only was used to detect endogenous and exogenous ONOO⁻ changes, but also enabled noninvasive visualization of ONOO⁻ generation in a different drug-induced DIALI model. We hope that these ratiometric probes can be useful chemical tools for the in-depth research of drug-induced acute hepatotoxicity.

中文翻译：

一种用于药物性急性肝损伤过程中过氧亚硝酸盐成像的高选择性比率分子探针

药物性急性肝损伤 (DIALI) 是一种常见的肝脏疾病，影响着全世界许多人，发病率每年都在增加。因此，开发新的干预和诊断工具至关重要。过氧亚硝酸盐 (ONOO ^- ) 是一种高活性物质，在 DIALI 过程中起着重要作用。因此，内源性ONOO ^-水平的原位分子成像对于检测ONOO ^-非常重要。在这项工作中，我们提出了两种破坏型比率荧光探针，AHC和AHMC，通过使用分子杂交策略进行 ONOO ^-检测。探头AHMC是通过将酯结构直接引入AHC以增强其对活细胞成像的膜穿透性而开发的。与其他活性物质相比，探针AHC对 ONOO ^-表现出良好的分析性能，具有低检测限 (≈1.8 nM) 和强比率荧光响应 (134 倍)。在细胞成像实验中，AHMC表现出优异的选择性、良好的生物相容性和线粒体靶向能力，不仅可用于检测内源性和外源性ONOO-变化^，还可以实现ONOO-的无创可视化^。在不同的药物诱导的 DIALI 模型中生成。我们希望这些比率探针可以成为深入研究药物引起的急性肝毒性的有用化学工具。

更新日期：2021-09-09

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