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用于在活细胞和非酒精性脂肪肝组织中高保真追踪脂滴的近红外荧光探针的工程化。

Engineering of a NIR fluorescent probe for high-fidelity tracking of lipid droplets in living cells and nonalcoholic fatty liver tissues.

机构信息

National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan, 430079, China.

National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan, 430079, China.

出版信息

Biosens Bioelectron. 2023 Nov 15;240:115646. doi: 10.1016/j.bios.2023.115646. Epub 2023 Aug 29.

DOI:10.1016/j.bios.2023.115646
PMID:37657311
Abstract

LDs (Lipid droplets) are key organelles for lipid metabolism and storage, which are closely related to ferroptosis and fatty liver. Due to its small size and highly dynamic nature, developing high-fidelity fluorescent probes for imaging of LDs is crucial for observing the dynamic physiological processes of LDs and investigating LDs-associated diseases. Herein, we synthesized three dicyanoisophorone-based fluorescent probes (DCIMe, DCIJ, and DCIQ) with different electron-donating groups and studied their imaging performance for LDs. The results show that DCIQ is highly polarity sensitive and can perform high-fidelity imaging for LDs, with significantly better performance than DCIMe, DCIJ, and commercial LD probe BODIPY 493/503. Based on this, DCIQ was successfully applied to real-time observe the interplays between LDs and other organelles (mitochondria, lysosomes, and endoplasmic reticulum), and to image the dynamics of LDs with fast scanning mode (0.44 s/frame) and the generation of oleic acid-induced LDs with high-fidelity. Finally, DCIQ was used to study the changes of LDs in the ferroptosis process and nonalcoholic fatty liver disease tissues. Overall, this study provided a powerful tool for high-fidelity imaging of LDs in cells and tissues.

摘要

LDs(脂质滴)是脂质代谢和储存的关键细胞器,与铁死亡和脂肪肝密切相关。由于其体积小且动态性质高,开发用于成像 LDs 的高保真荧光探针对于观察 LDs 的动态生理过程和研究 LDs 相关疾病至关重要。在此,我们合成了三种基于二氰异佛尔酮的荧光探针(DCIMe、DCIJ 和 DCIQ),它们具有不同的供电子基团,并研究了它们对 LDs 的成像性能。结果表明,DCIQ 对极性高度敏感,可对 LDs 进行高保真成像,性能明显优于 DCIMe、DCIJ 和商业 LD 探针 BODIPY 493/503。基于此,DCIQ 成功应用于实时观察 LDs 与其他细胞器(线粒体、溶酶体和内质网)之间的相互作用,以及使用快速扫描模式(0.44s/帧)对 LDs 的动力学进行高保真成像,并生成油酸诱导的 LDs。最后,DCIQ 用于研究铁死亡过程和非酒精性脂肪肝组织中 LDs 的变化。总的来说,这项研究为细胞和组织中 LDs 的高保真成像提供了有力的工具。

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