Mitochondria-localized dinuclear iridium(III) complexes for two-photon photodynamic therapy.

Photodynamic therapy (PDT), as a non-invasive cancer treatment, offers significant advantages including high temporal-spatial selectivity, minimal surgical intervention, and low toxicity, thereby garnering considerable research interest from across the world. In this study, we have developed a series of dinuclear cyclometalated Ir(III) complexes as potential two-photon photodynamic anticancer agents. These Ir(III) complexes demonstrate significant two-photon absorption (2PA) cross-sections ( = 66-166 GM) and specifically target mitochondria. Amongst them, N-Ir4 manifests an IC value of 2.0 μM and a phototoxicity index (PI) of 24. Under two-photon excitation, N-Ir4 efficiently generates reactive oxygen species (ROS), leading to mitochondrial damage and cell death. Our study reveals drastically enhanced optical properties forged by forming a dinuclear complex bridged by two conjugated rigid planar moieties and sheds light on a potential paradigm to boost 2PA cross-sections.