Wang Qian, Li Dongmei, Zhang Ze, Shen Lingyi, Xu Hong, Wang Zhiyong, Redshaw Carl, Zhang Qilong
Translational Medicine Research Center, Guizhou Medical University, Guiyang 550025, PR China.
School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, PR China.
Spectrochim Acta A Mol Biomol Spectrosc. 2025 Apr 5;330:125694. doi: 10.1016/j.saa.2024.125694. Epub 2025 Jan 2.
Non-alcoholic fatty liver disease (NAFLD) is a disease closely associated with metabolic abnormalities. Lipid droplets (LDs) serve as organelles that store intracellular neutral lipids and maintain cellular energy homeostasis. Their abnormalities can cause metabolic disorders and disease, which is also one of the distinctive characteristics of NAFLD patients. However, the correlation between the polarity of LDs and NAFLD is easily overlooked. To monitor the polarity changes in LDs in order to assess the progression of NAFLD, triphenylamine was used as the electron donor (D), pyridine as the electron acceptor (A) and thiazolo[5,4-d]thiazole (TTz) as π bridge in this study. The structure was modified by introducing different substituents at the triphenylamine to obtain a series of D-π-A structural polar-responsive asymmetric thiazolo[5,4-d]thiazole (aTTz) fluorescent probes with different push-pull electron effects and steric hindrance. The fluorescent probes, which exhibit distinct fluorescence emission spectra in solutions with varying polarities, demonstrate excellent polarity-sensitive properties, and the displacement of the maximum emission wavelength varies from 125 to 150 nm. Meanwhile, the fluorescent probes exhibited low dark toxicity of cells and can specifically image lipid droplets, with a localization coefficient of more than 0.84 when imaging, and can be applied to the fluorescence imaging of C. elegans. Furthermore, the polar response properties of the fluorescent probes were used to distinguish normal liver tissue and nonalcoholic fatty liver tissue by fluorescence lifetime microscopic imaging (FLIM), thus providing a molecular tool for the diagnosis of NAFLD.
非酒精性脂肪性肝病（NAFLD）是一种与代谢异常密切相关的疾病。脂滴（LDs）作为储存细胞内中性脂质并维持细胞能量稳态的细胞器。它们的异常会导致代谢紊乱和疾病，这也是NAFLD患者的显著特征之一。然而，脂滴极性与NAFLD之间的相关性很容易被忽视。为了监测脂滴的极性变化以评估NAFLD的进展，本研究使用三苯胺作为电子供体（D），吡啶作为电子受体（A），噻唑并[5,4-d]噻唑（TTz）作为π桥。通过在三苯胺上引入不同取代基对结构进行修饰，得到了一系列具有不同推挽电子效应和空间位阻的D-π-A结构的极性响应不对称噻唑并[5,4-d]噻唑（aTTz）荧光探针。这些荧光探针在不同极性的溶液中表现出明显不同的荧光发射光谱，具有优异的极性敏感特性，最大发射波长的位移在125至150nm之间。同时，荧光探针表现出较低的细胞暗毒性，能够特异性地对脂滴进行成像，成像时定位系数大于0.84，并且可应用于秀丽隐杆线虫的荧光成像。此外，利用荧光探针的极性响应特性，通过荧光寿命显微成像（FLIM）区分正常肝组织和非酒精性脂肪性肝组织，从而为NAFLD的诊断提供了一种分子工具。
