基于质谱和荧光成像的药物协同作用双模式精确可视化。

IF 6.7 1区 化学 Q1 CHEMISTRY, ANALYTICAL Analytical Chemistry Pub Date : 2024-11-19 Epub Date: 2024-11-05 DOI:10.1021/acs.analchem.4c03848
Jinlong Zhang, Yida Zhang, Taihe Han, Shuai Mu, Duolong Di, Xuezhao Shi, Xiaoyan Liu, Haixia Zhang
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引用次数: 0

摘要

非甾体类消炎药与硫化氢(H2S)之间可能存在协同效应,但缺乏直接的研究证据。使用单一的荧光检测方法很难准确确认协同效应的有效性。在这项研究中,荧光探针和非甾体抗炎药萘普生通过不同的自巯基间隔基团结合在一起,得到了一种可释放 H2S 的诊断和治疗一体化荧光探针 Nap-NP-NSB。通过监测细胞炎症和胃黏膜细胞氧化损伤的治疗过程,证实了 H2S 和萘普生的协同作用。最后,在急性肝炎小鼠模型中对肝脏和胃组织及其切片进行了活体荧光成像和质谱成像。双模态检测方法不仅证实了萘普生-萘磺酸具有更好的抗炎活性和更小的胃黏膜损伤,还能更准确地观察到萘普生和 H2S 的药物协同效应。这项工作提供了一种结合荧光成像和质谱成像的双重可视化成像方法,为研究基于自惰性结构的药物协同作用开拓了新思路。
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Dual-Modality Accurate Visualization of Drug Synergy Based on Mass Spectrometry and Fluorescence Imaging.

There is a potential synergistic effect between nonsteroidal anti-inflammatory drugs and hydrogen sulfide (H2S), but direct evidence for the study is lacking. With a single fluorescence detection method, it is difficult to accurately confirm the effectiveness of the synergistic effect. In this study, the fluorescent probe and the nonsteroidal anti-inflammatory drug naproxen were combined via different self-immolative spacer groups to obtain a diagnostic and therapeutic integrated fluorescent probe Nap-NP-NSB, which can release H2S. The quantitative release of H2S by Nap-NP-NSB was evaluated in vitro and in cells, and the synergistic effect of H2S and naproxen was confirmed by monitoring the treatment process of cellular inflammation and oxidative damage of gastric mucosa cells. Finally, in vivo fluorescence imaging and mass spectrometry imaging of the liver and stomach tissues and their sections were performed in the mouse model of acute hepatitis. The dual-modal detection method not only confirmed that Nap-NP-NSB had better anti-inflammatory activity and less gastric mucosal damage, but also enabled a more accurate visualization of the drug synergistic effect of naproxen and H2S. This work provides a dual visualization imaging method combining fluorescence and mass spectrometry imaging and develops a new idea for studying drug synergies based on self-immolative structures.

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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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