TY - JOUR
T1 - A Bivalent Iridium(III) Complex Toolkit for Mitochondrial DNA G-Quadruplex-Targeted Theranostics
AU - Xu, Yiwen
AU - Wang, Ling
AU - Du, Jianxiong
AU - Shiu-Hin Chan, Daniel
AU - Wu, Lei
AU - Jia, Mengzhao
AU - Liu, Jin-Biao
AU - Wong, Chun-Yuen
AU - Yang, Kai
AU - Leung, Chung-Hang
AU - Wang, Wanhe
PY - 2025/4/22
Y1 - 2025/4/22
N2 - The G-quadruplex (G4) is an important diagnostic and therapeutic target in cancers, but the development of theranostic probes for subcellular G4 s 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, where complex 3 exhibited a 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. © 2025 Wiley-VCH GmbH.
AB - The G-quadruplex (G4) is an important diagnostic and therapeutic target in cancers, but the development of theranostic probes for subcellular G4 s 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, where complex 3 exhibited a 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. © 2025 Wiley-VCH GmbH.
KW - Imaging
KW - Iridium(III) complex
KW - mitochondrial G-quadruplex
KW - NIR
KW - PDT
UR - http://www.scopus.com/inward/record.url?scp=105003278047&partnerID=8YFLogxK
UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-105003278047&origin=recordpage
U2 - 10.1002/chem.202403853
DO - 10.1002/chem.202403853
M3 - RGC 21 - Publication in refereed journal
SN - 0947-6539
VL - 31
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 23
M1 - e202403853
ER -
