A coumarin-based TICT fluorescent probe for real-time fluorescence lifetime imaging of mitochondrial viscosity and systemic inflammation in vivo,Journal of Materials Chemistry B

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A coumarin-based TICT fluorescent probe for real-time fluorescence lifetime imaging of mitochondrial viscosity and systemic inflammation in vivo
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2021-08-18 , DOI: 10.1039/d1tb01150b
Yun Liang ₁ , Yuping Zhao ₁ , Chaofeng Lai ₁ , Xiang Zou ₁ , Weiying Lin ₁

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Systemic inflammation, linked with abnormal mitochondrial viscosity, is reported to be associated with cerebro-cardiovascular disease and Alzheimer's disease. Therefore, it is of great significance to detect the mitochondrial viscosity to indicate the inflammatory signal in vivo. Considering the strategies of fluorescent molecular rotors (FMRs) and fluorescence lifetime imaging microscopy (FLIM), we have rationally designed a novel mitochondrial viscosity-specific fluorescent probe Mito-VCI, based on coumarin fluorophores with benzo[e]indolium as the rotor group. In a high viscosity solution system, the fluorescence lifetime of the probe Mito-VCI was prolonged due to the planarization and rigidity enhancement of the molecular rotor. Satisfactorily, the probe was only sensitive to viscosity, instead of non-viscosity factors such as pH and polarity. Furthermore, the probe sensitively targeted mitochondria in HeLa cells with a Pearson's correlation of 0.93, and specifically detected dynamics variation of mitochondrial viscosity with FLIM imaging in HeLa cells induced by LPS. Notably, significant fluorescence lifetime changes of Mito-VCI between normal and inflammatory tissues also occurred (for example, the fluorescence lifetime in the spleen changed from 1.128 to 1.432 ns). It can be inferred from the above observations that Mito-VCI could work as an effective and sensitive fluorescent molecular rotor for mitochondrial viscosity monitoring through FLIM imaging with a systemic inflammatory response, and provide potential applications for the diagnosis of systemic inflammation in pharmacology and toxicology studies.

中文翻译：

一种基于香豆素的 TICT 荧光探针，用于体内线粒体粘度和全身炎症的实时荧光寿命成像

据报道，与线粒体粘度异常有关的全身性炎症与脑心血管疾病和阿尔茨海默病有关。因此，检测线粒体粘度对指示体内炎症信号具有重要意义。考虑到荧光分子转子（FMRs）和荧光寿命成像显微镜（FLIM）的策略，我们以苯并[ e ]吲哚为转子基团的香豆素荧光团，合理设计了一种新型线粒体粘度特异性荧光探针Mito-VCI 。在高粘度溶液系统中，Mito-VCI探针的荧光寿命由于分子转子的平面化和刚性增强，延长了。令人满意的是，探头只对粘度敏感，而不是非粘度因素，如 pH 值和极性。此外，该探针敏感地靶向 HeLa 细胞中的线粒体，皮尔逊相关系数为 0.93，并通过 LPS 诱导的 HeLa 细胞中的 FLIM 成像特异性检测线粒体粘度的动态变化。值得注意的是，正常组织和炎症组织之间Mito-VCI的荧光寿命也发生了显着变化（例如，脾脏中的荧光寿命从 1.128 变为 1.432 ns）。从以上观察可以推断出Mito-VCI可以作为一种有效且灵敏的荧光分子转子，通过具有全身炎症反应的 FLIM 成像监测线粒体粘度，并为药理学和毒理学研究中的全身炎症诊断提供潜在应用。

更新日期：2021-09-07

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