<br>比率近红外荧光探针通过对线粒体中的 HClO 进行成像来监测 HCC 细胞的铁死亡,Analytical Chemistry

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比率近红外荧光探针通过对线粒体中的 HClO 进行成像来监测 HCC 细胞的铁死亡
Analytical Chemistry ( IF 6.7 ) Pub Date : 2024-04-04 , DOI: 10.1021/acs.analchem.4c00328
Bo Zhao ₁ , Xionghao Xu ₁ , Xin Wen ₁ , Qingqing Liu ₁ , Chao Dong ₁ , Qingkun Yang ₂ , Chunhua Fan ₁ , Juyoung Yoon ₃ , Zhengliang Lu ₁

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次氯酸（HClO）是一种典型的内源性ROS，主要在线粒体中产生，具有很强的氧化特性。 HClO 水平异常会导致线粒体功能障碍，与多种疾病密切相关。研究表明，HClO 在铁死亡和肝细胞癌 (HCC) 细胞中均显示出过度表达的痕迹。因此，HCC 铁死亡过程中 HClO 水平的可视化对于探索其生理和病理作用非常重要。迄今为止，尚无HClO在HCC铁死亡中可视化的报道。因此，我们提出了一种比率近红外 (NIR) 荧光探针Mito-Rh-S ，它首次可视化 HCC 铁死亡过程中线粒体中 HClO 的波动。 Mito-Rh-S具有超快的响应速率（2 s）和大的发射位移（115 nm）。 Mito-Rh-S是基于PET传感机制构建的，因此具有高信噪比。 Mito-Rh-S的细胞实验表明，Fe ²⁺和erastin诱导的HepG2细胞中的铁死亡导致线粒体HClO水平升高，高浓度的Fe ²⁺和erastin会导致严重的线粒体损伤和氧化应激，并导致线粒体损伤和氧化应激。具有杀死 HepG2 细胞的潜力。通过调节erastin浓度、erastin诱导时间以及对铁死亡模型的处理， Mito-Rh-S可以准确检测HCC铁死亡过程中线粒体HClO水平的波动。

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Ratiometric Near-Infrared Fluorescent Probe Monitors Ferroptosis in HCC Cells by Imaging HClO in Mitochondria

Hypochlorous acid (HClO) is a typical endogenous ROS produced mainly in mitochondria, and it has strong oxidative properties. Abnormal HClO levels lead to mitochondrial dysfunction, strongly associated with various diseases. It has been shown that HClO shows traces of overexpression in cells of both ferroptosis and hepatocellular carcinoma (HCC). Therefore, visualization of HClO levels during ferroptosis of HCC is important to explore its physiological and pathological roles. So far, there has been no report on the visualization of HClO in ferroptosis of HCC. Thus, we present a ratiometric near-infrared (NIR) fluorescent probe Mito-Rh-S which visualized for the first time the fluctuation of HClO in mitochondria during ferroptosis of HCC. Mito-Rh-S has an ultrafast response rate (2 s) and large emission shift (115 nm). Mito-Rh-S was constructed based on the PET sensing mechanism and thus has a high signal-to-noise ratio. The cell experiments of Mito-Rh-S demonstrated that Fe²⁺- and erastin-induced ferroptosis in HepG2 cells resulted in elevated levels of mitochondrial HClO and that high concentration levels of Fe²⁺ and erastin cause severe mitochondrial damage and oxidative stress and had the potential to kill HepG2 cells. By regulating the erastin concentration, erastin induction time, and treatment of the ferroptosis model, Mito-Rh-S can accurately detect the fluctuation of mitochondrial HClO levels during ferroptosis in HCC.

更新日期：2024-04-04

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