Steric hindrance engineering on Iridium(III) photosensitizers: unlocking aggregation-induced emission for enhanced photodynamic therapy.

Ir(III) complexes have gained significant attention as photosensitizers (PSs) in fluorescence imaging-guided photodynamic therapy (PDT) due to their tunable structures and rich photophysical properties. However, the development of Ir(III)-based PSs that possess both strong emission and high reactive oxygen species (ROS) generation capabilities in the biological microenvironment still remains challenges. Herein, we propose a rational molecular design strategy to concurrently boost both photoluminescence and ROS generation in Ir(III)-based PSs through steric hindrance engineering. The introduction of bulky aromatic groups effectively activates aggregation-induced emission (AIE) in aggregate state by restricting molecular motion. The reference Ir(III) complex Ir-HP was prepared with 1,10-phenanthroline and phenylpyridine as the ancillary and cyclometalating ligands, respectively. To systematically modulate steric hindrance and electron-donating properties, pyrrole, indole, and carbazole moieties were incorporated into the ancillary ligand, effectively adjusting solid-state packing and excited-state behavior of the resulting complexes. Among them, the carbazole-functionalized Ir-CP exhibited pronounced AIE characteristics and a red-shifted emission. Furthermore, the large spin-orbit coupling endowed Ir-CP with superior ROS production, which is highly advantageous for fluorescence imaging-guided PDT applications. Water-soluble Ir-CP nanoparticles demonstrated excellent phototoxicity against cancer cells and efficiently suppressed tumor growth in vivo. Additionally, these nanoparticles showed the capability to inactivate the rabies virus via PDT, highlighting their potential for a wide range of biomedical applications.