Bingbing Chen, Zhijun Liang, Yao Gong, Wei Wu, Jiaen Huang, Jiaxi Chen, Yanmei Wang, Jun Mei, Rui Chen, Zunnan Huang, Jing Sun
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引用次数: 0
摘要
线粒体粘度已成为癌症和神经退行性疾病等疾病的一种有前景的生物标志物,但在亚细胞水平准确测量粘度仍是一项重大挑战。在这项研究中,我们合成并鉴定了三种以 5-氟尿嘧啶衍生物为配体的环金属化铱(III)配合物(Ir1-Ir3)。其中,Ir1 通过增加线粒体产生的活性氧(ROS)选择性地诱导 HeLa 细胞凋亡,从而引发一连串导致线粒体功能障碍的事件。此外,Ir1 的荧光寿命对细胞内粘度变化的敏感性很高,因此可以对细胞凋亡过程中的细胞微粘度进行实时荧光寿命成像显微镜(FLIM)观察。这些发现强调了环金属化 Ir(III)复合物在亚细胞水平的治疗和诊断应用潜力。
Mitochondrial viscosity probes: iridium(III) complexes induce apoptosis in HeLa cells.
Mitochondrial viscosity has emerged as a promising biomarker for diseases such as cancer and neurodegenerative disorders, yet accurately measuring viscosity at the subcellular level remains a significant challenge. In this study, we synthesized and characterized three cyclometalated iridium(III) complexes (Ir1-Ir3) containing 5-fluorouracil derivatives as ligands. Among these, Ir1 selectively induced apoptosis in HeLa cells by increasing mitochondrial production of reactive oxygen species (ROS), which triggered a cascade of events leading to mitochondrial dysfunction. Additionally, the fluorescence lifetime of Ir1 demonstrated high sensitivity to intracellular viscosity changes, enabling real-time fluorescence lifetime imaging microscopy (FLIM) of cellular micro-viscosity during apoptosis. These findings underscore the potential of cyclometalated Ir(III) complexes for both therapeutic and diagnostic applications at the subcellular level.