MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University , Guangzhou 510275, P. R. China.
ACS Appl Mater Interfaces. 2017 Apr 19;9(15):13304-13314. doi: 10.1021/acsami.7b01735. Epub 2017 Apr 6.
Phosphorescent Ir(III) complexes are expected to be new multifunctional theranostic platforms that enable the integration of imaging capabilities and anticancer properties. Mitophagy is an important selective autophagic process that degrades dysfunctional mitochondria. Until now, the regulation of mitophagy is still poorly understood. Herein, we present two phosphorescent cyclometalated iridium(III) complexes (Ir1 and Ir2) that can accumulate in mitochondria and induce mitophagy. Because of their intrinsic phosphorescence, they can specially image mitochondria and track mitochondrial morphological alterations. Mechanism studies show that Ir1 and Ir2 induce mitophagy by depolarization of mitochondrial membrane potential, depletion of cellular ATP, perturbation in mitochondrial metabolic status, and induction of oxidative stress. Moreover, no sign of apoptosis is observed in Ir1- and Ir2-treated cells under the same conditions that an obvious mitophagic response is initiated. We demonstrate that Ir1 is a promising theranostic agent that can induce mitophagy and visualize changes in mitochondrial morphology simultaneously.
磷光铱(III)配合物有望成为新的多功能治疗平台，实现成像功能和抗癌特性的整合。线粒体自噬是一种重要的选择性自噬过程，可降解功能失调的线粒体。到目前为止，线粒体自噬的调控仍知之甚少。在此，我们介绍了两种可聚集在线粒体中并诱导线粒体自噬的磷光环金属铱(III)配合物（Ir1 和 Ir2）。由于它们具有内在的磷光特性，因此可以专门对线粒体进行成像并跟踪线粒体形态的变化。机制研究表明，Ir1 和 Ir2 通过线粒体膜电位去极化、细胞 ATP 耗竭、线粒体代谢状态紊乱和氧化应激诱导来诱导线粒体自噬。此外，在相同条件下，在用 Ir1 和 Ir2 处理的细胞中未观察到凋亡的迹象，而在相同条件下则启动了明显的线粒体自噬反应。我们证明 Ir1 是一种很有前途的治疗剂，它可以诱导线粒体自噬并同时可视化线粒体形态的变化。
