A Bivalent Iridium(III) Complex Toolkit for Mitochondrial DNA G‐Quadruplex‐Targeted Theranostics

The G‐quadruplex (G4) is an important diagnostic and therapeutic target in cancers, but the development of theranostic probes for subcellular G4s remains challenging. In this work, we report three G4‐targeted theranostic probes by conjugating a pyridostatin‐derived G4 ligand to G4‐specific iridium(III) complexes with desirable photophysical properties. These probes showed specifically enhanced luminescence to mitochondrial G4 in triple negative breast cancer (TNBC) cells. Of note, complex 3 exhibited NIR emission and the ability to discriminate TNBC cells and normal breast cells. Furthermore, these probes showed much higher PDT toxicity in TNBC cells through ROS‐induced apoptosis, in which complex 3exhibited type I/II hybrid PDT effect with the potential to overcome hypoxia. These results demonstrate that these complexes are multicolor and modular phototheranostic probes for DNA G4s. We believe that this work offers a multifunctional theranostic toolkit for unmasking subcellular DNA G‐quadruplex functions.