Microstructural regulation of Ir(III) complexes for enhanced photocytotoxicity in photodynamic cancer therapy

Malignant tumors continue to be the most common and remain one of the leading causes of death with increasing incidence, mortality, and burden. Traditional chemotherapeutic agents often encounter significant side effects and demonstrate lackluster efficacy. Photodynamic therapy (PDT) is widely recognized as a microtrauma therapeutic method for tumor treatment technique. Ir(III) complexes are a potential photosensitizer (PS) type due to their excellent photophysical properties. Ir-1 and Ir-2, which are two novel Ir(III) complexes were synthesized and characterized using spectroscopic and electrochemical techniques, the key structural difference lies in the position of a benzene in the C^N ligand. This slight change makes Ir-2 have a better intersystem crossing (ISC) ability and thus has more excellent triplet excited state properties. So Ir-2 shows high singlet oxygen (¹O₂) production and photocytotoxicity with half maximal inhibitory concentration (IC₅₀) of 40 nM, effectively inhibiting and eliminating tumors in mice while demonstrating good biosafety. This study highlights the importance of precise molecular design in developing highly efficient PSs for PDT.