He Xiaojun, Zheng Ziman, Zhang Feifan, Xu Chuchu, Xu Wei, Ye Lisong, Sun Xiaoshuai, Zhou Zhan, Shen Jianliang
School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Luoyang Key Laboratory of Organic Functional Molecules, College of Food and Drug, Luoyang Normal University, Luoyang 471934, China.
ACS Appl Bio Mater. 2020 Nov 16;3(11):7886-7897. doi: 10.1021/acsabm.0c01029. Epub 2020 Sep 17.
Bioactive molecules play a vital role in the process of regulating the redox balance in the intracellular environment, especially in maintaining the function of organelles. To explore the association and function of bioactive molecules in organelles, it is essential to develop a chemosensor tool that uses multiresponse fluorescence signals to distinguish between and track two related bioactive molecules in organelles. However, the development of sensors with multiresponse functions is still a challenging task. Herein, we present a unique and practical single chemosensor () that can monitor HClO (as an oxidative substance) and HS (as a reductive substance) in mitochondria (organelle targeting) with multiresponse fluorescence signals. The response of the sensor to HClO and HS changes from red to green and blue channel emission simultaneously, respectively, thereby providing a specific signal response to reductive/oxidative substances in the mitochondria. Using a single chemosensor, we have realized multichannel bioimaging of the exogenous and endogenous HClO and HS in cellular mitochondria. Additionally, the excellent properties of the sensor can be used to reveal the relationship between HClO and HS in mitochondria. Meanwhile, has been endowed with the ability to image in bacteria and zebrafish attributed to the good permeability and low cytotoxicity. Expectantly, drug-induced liver injury (DILI) caused by fluoxetine (an antidepressant drug) and the degree of drug-induced toxicity to the liver were evaluated using through discriminating and imaging HClO, indicating that has the potential function of evaluating the toxicity of the drug to the liver.
生物活性分子在调节细胞内环境中的氧化还原平衡过程中起着至关重要的作用,特别是在维持细胞器功能方面。为了探索生物活性分子在细胞器中的关联和功能,开发一种化学传感器工具至关重要,该工具利用多响应荧光信号来区分和追踪细胞器中的两种相关生物活性分子。然而,开发具有多响应功能的传感器仍然是一项具有挑战性的任务。在此,我们提出了一种独特且实用的单一化学传感器(),它可以通过多响应荧光信号监测线粒体(细胞器靶向)中的HClO(作为一种氧化物质)和HS(作为一种还原物质)。该传感器对HClO和HS的响应分别同时从红色变为绿色和蓝色通道发射,从而为线粒体中的还原/氧化物质提供特定的信号响应。使用单一化学传感器,我们实现了细胞线粒体外源性和内源性HClO和HS的多通道生物成像。此外,该传感器的优异特性可用于揭示线粒体中HClO和HS之间的关系。同时,由于其良好的渗透性和低细胞毒性,已赋予其在细菌和斑马鱼中成像的能力。预期,通过区分和成像HClO,使用来评估由氟西汀(一种抗抑郁药物)引起的药物性肝损伤(DILI)以及药物对肝脏的毒性程度,表明具有评估药物对肝脏毒性的潜在功能。