Abstract:
Lipid droplets (LDs) dysfunction is closely associated with a multitude of diseases, including nonalcoholic fatty liver disease (NAFLD). Therefore, it is imperative to develop fluorescent probes that specifically target LDs for the early detection and diagnosis of NAFLD. In this study, a series of lipophilic fluorophores CZ1-CZ4 that feature a D-π-A configuration were designed and synthesized based on the carbazole and tricocyanofuran derivatives. The photophysical data revealed that all four probes exhibited large Stokes shifts (~ 120 nm) in high-polarity solvents (e.g., DMSO) and demonstrated enhanced fluorescence in solvents ranging from low-polarity (e.g., 1,4-Dioxane) to high-polarity. Notably, by utilizing probe CZ1, we could specifically visualize LDs and captured high-quality images, even eliminating the need for a time-consuming wash procedure. Moreover, CZ1 enabled monitoring of LDs dynamic changes in-real time within live cells, and importantly, it could be used to effectively distinguish normal and NAFLD tissues at both the organ and in vivo level. This exceptional property of probe CZ1 provides a practical tool for the diagnosis and intervention of NAFLD.
摘要:
脂滴(LDs)功能障碍与多种疾病密切相关,包括非酒精性脂肪性肝病(NAFLD)。因此,开发特异性靶向LDs的荧光探针用于NAFLD的早期检测和诊断是当务之急。在这项研究中,基于咔唑和三氰呋喃衍生物,设计并合成了一系列具有D-π-A构型的亲脂性荧光团CZ1-CZ4。光物理数据表明,所有四个探针在高极性溶剂中都表现出大的斯托克斯位移(〜120nm)(例如,DMSO),并在低极性范围的溶剂中表现出增强的荧光(例如,1,4-二恶烷)至高极性。值得注意的是,通过利用探头CZ1,我们可以专门可视化LD并捕获高质量图像,甚至消除了耗时的清洗程序的需要。此外,CZ1能够实时监测活细胞内LD的动态变化,而且重要的是,它可用于在器官和体内水平上有效区分正常和NAFLD组织。探针CZ1的这种特殊性质为NAFLD的诊断和干预提供了实用工具。