Engineering iridium(III) complexes for enhancing electron transfer-based photodynamic therapy

The lower oxygen dependence of Type I photodynamic therapy (PDT), which functions via photoinduced electron transfer, has garnered considerable research interest in recent years. Iridium(III) complexes, characterized by their strong spin-orbit coupling, long-lived excited states, versatile and easy tunable photophysical properties-features that are essential for facilitating triplet-involved photoreactions have shown great promise as platforms for developing high-performance Type I photosensitizers (PSs). In contrast to previous reviews covering a wide range of PSs, this article focuses specifically on iridium(III) complex-based systems, and methodically outline key molecular design strategies aimed at boosting Type I photoreactivity, including the construction of diverse donor-acceptor type ligands, cooperative effects of multiple ligands, utilization of multiple heavy atoms, incorporation of chromophores into iridium(III), and employing ligands with reactive hydrogen for proton-coupled electron transfer. Finally, the current challenges and prospective solutions in translating iridium(III) complexes from fundamental research into clinical applications are discussed. It is hoped that this review will aid in the development of novel, efficient, and hypoxia-tolerant metal-complex-based PSs and thus facilitate the clinical advancement of PDT. This review presents a systematic overview of iridium(III) complexes for improved electron transfer-based photodynamic therapy, emphasizing molecular design methodologies and analysis of the underlying mechanism. It provides critical insights and establishes a conceptual framework to guide the rational development of advanced photosensitizers based on metal complexes, thereby facilitating their accelerated translation from experimental research toward clinical application. • Design methodologies to improve the photoinduced electron transfer in phototherepy of iridium(III) complexes are emphasized. • Recent advancements about iridium(III) complexes with efficient type I photodynamic therapy are presented. • Future directions for accelerating iridium(III) complexes from researches to clinical use are discussed.