Guanidine-modified cyclometalated iridium(III) complexes for mitochondria-targeted imaging and photodynamic therapy

PDT is a well-established therapeutic modality for many types of cancer. Photoluminescent cyclometalated iridium(III) complexes are one of the most commonly used classes of organometallic compounds with potential beneficial applications in bioimaging and as promising anticancer agents. In the present study, three new cyclometalated iridium(III) complexes (Ir1–Ir3) containing guanidinium ligands were found to exert excellent cytotoxic effects on different types of cancer cells upon light irradiation at 425 nm. Notably, Ir1 conferred almost no dark toxicity (IC50 > 100 μM) to HepG2 cells, but the value decreased by 387-fold to 0.36 μM following 10 min of light irradiation (425 nm). Further mechanistic investigation revealed that complex Ir1 could induce apoptosis via the activation of reactive oxygen species (ROS)-mediated mitochondrial signaling pathways in the presence or absence of light irradiation. In vivo studies demonstrated that Ir1 significantly inhibited tumor growth in HepG2 xenograft-bearing mice under light irradiation at 425 nm. Taken together, these findings indicate that designing PDT-based Ir(III) complexes may hold a great deal of promise for anticancer drug development. [Display omitted] •Three Ir(III) complexes containing guanidinium ligands were synthesized.•Ir1 displayed higher phototoxicities to HepG2 cells upon irradiation at 425 nm.•Ir1 mainly located mitochondria in HepG2 cells.•In vivo studies, Ir1 has demonstrated the excellent anticancer efficacy irradiated with a 425 nm laser.