Fluorescent probes with dual-targeting organelles monitor polarity in non-alcoholic fatty liver disease

IF 4.3 2区化学 Q1 SPECTROSCOPY

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy Pub Date : 2024-11-19 DOI:10.1016/j.saa.2024.125455

Yi Deng , Jie Wang , Sichen Zhang , Jiale Li , Aobo Sun , Xue Zhang , Lei Hu , Chunfei Wang , Hui Wang

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Abstract

Non-alcoholic fatty liver disease (NAFLD) becomes a world health issue due to its rising prevalence and lack of a definitive pathogeny. However, the excessive accumulation of fat droplets has been recognized as a crucial characteristic of NAFLD, accompanied with endoplasmic reticulum stress in its onset and progression as well. Therefore, real-time monitoring the dynamic of lipid droplets (LDs) and endoplasmic reticulum (ER) within cells is paramount. In this regard, four D-A-π-D structural fluorescent probes COB1-COB4 were designed and synthesized wherein coumarin connected with carbazole acted as precursors while the side chains attached to carbazole groups are different. Here, probes COB1-COB4 exhibited high sensitivity towards polarity, while COB2 was chosen for further study attributing to its excellent anti-interference property. Cell imaging demonstrated that COB2 could accurately target both LDs and ER at the same time and monitor the changes of the two organelles under different physiological conditions. Notably, probe COB2 also exhibited the ability to distinguish normal liver from fatty liver at the tissue level. The above results lay an experimental foundation for developing novel dual-targeted probes with potential for early diagnosis of non-alcoholic fatty liver.

Abstract Image

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具有双靶向细胞器的荧光探针可监测非酒精性脂肪肝的极性。

非酒精性脂肪肝（NAFLD）因其发病率不断上升和缺乏明确的病原体而成为一个世界性的健康问题。然而，脂肪滴的过度积聚已被认为是非酒精性脂肪肝的一个重要特征，在其发生和发展过程中还伴有内质网应激。因此，实时监测细胞内脂滴（LDs）和内质网（ER）的动态至关重要。为此，我们设计并合成了四种 D-A-π-D 结构荧光探针 COB1-COB4，其中香豆素与咔唑相连作为前体，而连接到咔唑基团的侧链则各不相同。其中，探针 COB1-COB4 对极性具有高灵敏度，而 COB2 则因其出色的抗干扰性能而被选作进一步研究的对象。细胞成像结果表明，COB2 可以同时准确地靶向 LD 和 ER，并监测这两种细胞器在不同生理条件下的变化。值得注意的是，探针 COB2 还能在组织水平上区分正常肝脏和脂肪肝。上述结果为开发新型双靶向探针奠定了实验基础，有望用于非酒精性脂肪肝的早期诊断。

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来源期刊

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 物理-光谱学

CiteScore

8.40

自引率

11.40%

发文量

1364

审稿时长

40 days

期刊介绍： Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy (SAA) is an interdisciplinary journal which spans from basic to applied aspects of optical spectroscopy in chemistry, medicine, biology, and materials science. The journal publishes original scientific papers that feature high-quality spectroscopic data and analysis. From the broad range of optical spectroscopies, the emphasis is on electronic, vibrational or rotational spectra of molecules, rather than on spectroscopy based on magnetic moments. Criteria for publication in SAA are novelty, uniqueness, and outstanding quality. Routine applications of spectroscopic techniques and computational methods are not appropriate. Topics of particular interest of Spectrochimica Acta Part A include, but are not limited to: Spectroscopy and dynamics of bioanalytical, biomedical, environmental, and atmospheric sciences, Novel experimental techniques or instrumentation for molecular spectroscopy, Novel theoretical and computational methods, Novel applications in photochemistry and photobiology, Novel interpretational approaches as well as advances in data analysis based on electronic or vibrational spectroscopy.