MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (P. R. China).
Angew Chem Int Ed Engl. 2014 Nov 3;53(45):12137-41. doi: 10.1002/anie.201407468. Epub 2014 Sep 22.
During autophagy, the intracellular components are captured in autophagosomes and delivered to lysosomes for degradation and recycling. Changes in lysosomal trafficking and contents are key events in the regulation of autophagy, which has been implicated in many physiological and pathological processes. In this work, two iridium(III) complexes (LysoIr1 and LysoIr2) are developed as theranostic agents to monitor autophagic lysosomes. These complexes display lysosome-activated phosphorescence and can specifically label lysosomes with high photostability. Simultaneously, they can induce autophagy potently without initiating an apoptosis response. We demonstrate that LysoIr2 can effectively implement two functions, namely autophagy induction and lysosomal tracking, in the visualization of autophagosomal-lysosomal fusion. More importantly, they display strong two-photon excited fluorescence (TPEF), which is favorable for live cell imaging and in vivo applications.
在自噬过程中,细胞内成分被捕获到自噬体中,并递送到溶酶体中进行降解和再循环。溶酶体运输和内容物的变化是自噬调节的关键事件,自噬与许多生理和病理过程有关。在这项工作中,开发了两种铱(III)配合物(LysoIr1 和 LysoIr2)作为治疗诊断试剂来监测自噬溶酶体。这些配合物显示出溶酶体激活的磷光,并可以特异性地用高光稳定性标记溶酶体。同时,它们可以强烈地诱导自噬而不引发细胞凋亡反应。我们证明 LysoIr2 可以有效地在自噬体-溶酶体融合的可视化中实现两个功能,即自噬诱导和溶酶体跟踪。更重要的是,它们显示出很强的双光子激发荧光(TPEF),这有利于活细胞成像和体内应用。