Novel Endoplasmic Reticulum-Targeted Luminescent Probe for Visualization of Carbon Monoxide in Drug-Induced Liver Injury.

IF 6.7 1区 化学 Q1 CHEMISTRY, ANALYTICAL
Analytical Chemistry Pub Date : 2024-11-12 Epub Date: 2024-11-03 DOI:10.1021/acs.analchem.4c04528
Deshu Kong, Yundi Huang, Bo Song, Xinyue Zhang, Jingli Yuan
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引用次数: 0

Abstract

Drug-induced liver injury (DILI) is a major hepatic dysfunction commonly caused by hepatotoxic drug overdose, resulting in a considerable number of fatalities worldwide. Recent studies have highlighted the regulatory and hepatoprotective effects of carbon monoxide (CO) during the liver injury process. However, precisely tracking the dynamic changes in the composition of CO in DILI is still a great challenge. In this work, leveraging the innovative "quencher-insertion" strategy, a unique endoplasmic reticulum (ER)-targetable lanthanide complex-based luminescence probe, ER-ANBTTA-Eu3+/Tb3+, has been developed for the selective and accurate monitoring of CO fluxes in live cells and laboratory animals. The new probe is composed of three covalently linked functional moieties: the terpyridine polyacid-Eu3+/Tb3+-mixed chelates as the long-lived luminophore, a p-toluenesulfonamide moiety as the ER-anchoring motif, and an allyloxy-nitrobenzyl ether moiety as the CO-specific recognition unit. Upon reaction with CO in the presence of Pd2+ ions, the Tsuji-Trost reaction leads to the cleavage of the allyloxy-nitrobenzyl group from the Eu3+/Tb3+-mixed chelates, which results in the restoration of Tb3+ emission at 538 nm and the attenuation of Eu3+ emission at 688 nm, leading to a dramatic increase of the I538/I688 ratio. In addition to the exceptional response sensitivity and selectivity toward CO, ER-ANBTTA-Eu3+/Tb3+ also exhibits the outstanding ER-locating capability, which allows the probe to be used for imaging of CO in the ER of live cells. Using this probe, combined with the time-gated luminescence imaging mode, the exogenous and endogenous CO in ER of live cells were monitored without the interference of background autofluorescence. Moreover, the upregulation of hepatic CO in DILI mice was successfully visualized. The results suggested the potential of ER-ANBTTA-Eu3+/Tb3+ for deeply exploring the functions of CO in DILI pathogenesis.

Abstract Image

用于药物性肝损伤中一氧化碳可视化的新型内质网靶向发光探针
药物性肝损伤(DILI)是一种主要的肝功能障碍,通常由肝毒性药物过量引起,在全球造成大量死亡。最近的研究强调了一氧化碳(CO)在肝损伤过程中的调节和保肝作用。然而,精确跟踪一氧化碳成分在 DILI 中的动态变化仍然是一个巨大的挑战。本研究利用创新的 "淬灭-插入 "策略,开发了一种独特的内质网(ER)可靶向镧系元素复合物发光探针--ER-ANBTTA-Eu3+/Tb3+,用于活细胞和实验动物中一氧化碳通量的选择性精确监测。这种新型探针由三个共价连接的功能分子组成:作为长寿命发光体的萜吡啶多酸-Eu3+/Tb3+混合螯合物、作为ER锚定基团的对甲苯磺酰胺分子以及作为CO特异性识别单元的烯丙氧基硝基苯醚分子。在 Pd2+ 离子存在下与 CO 反应时,辻-特罗斯特反应会导致 Eu3+/Tb3+ 混合螯合物中的烯丙氧基-硝基苄基裂解,从而恢复 Tb3+ 在 538 纳米波长的发射,衰减 Eu3+ 在 688 纳米波长的发射,使 I538/I688 比值显著增加。ER-ANBTTA-Eu3+/Tb3+ 除了对 CO 具有卓越的响应灵敏度和选择性外,还具有出色的 ER 定位能力,可用于活细胞 ER 中 CO 的成像。利用该探针,结合时间门控发光成像模式,可以监测活细胞ER中的外源性和内源性CO,而不受背景自发荧光的干扰。此外,还成功地观察到了 DILI 小鼠肝脏 CO 的上调。结果表明,ER-ANBTTA-Eu3+/Tb3+具有深入探索CO在DILI发病机制中的功能的潜力。
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来源期刊
Analytical Chemistry
Analytical Chemistry 化学-分析化学
CiteScore
12.10
自引率
12.20%
发文量
1949
审稿时长
1.4 months
期刊介绍: Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.
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