Enhanced ROS generation in AIE-active iridium(iii) photosensitizers by cationization engineering for advanced photodynamic therapy†

Phosphorescent iridium(III) complexes have emerged as promising photosensitizers (PSs) for clinical photodynamic therapy (PDT) due to their notable antitumor efficacy. However, their practical application is hindered by weak emission in aggregated states and insufficient reactive oxygen species (ROS) generation. In this study, we present a straightforward cationization strategy aimed at simultaneously enhancing both the emission and ROS production of Ir(III)-based PSs. Two Ir(III) complexes PPI-C1 and PPI-C2 which feature an incremental number of hexafluorophosphate counterions were strategically designed through simple ligand engineering of the neutral precursor PPI-C0. Both experimental and theoretical analyses reveal that cationization effectively modulates the aggregate behavior and excited-state properties of these complexes, with PPI-C2 displaying a significantly improved AIE characteristic and effective intersystem crossing ability. As expected, the water-soluble PPI-C2 nanoparticles showed superior ROS production and good biocompatibility under light irradiation, leading to cell apoptosis and significant inhibition of tumor growth in vivo. This study will offer new insights into the design of effective AIE-active Ir(III)-based photosensitizers for PDT.