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

Abstract

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 (σ₂ = 66–166 GM) and specifically target mitochondria. Amongst them, N-Ir4 manifests an IC₅₀ 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.