Unveiling photophysical mechanisms of NIR-II AIE luminogens for multimodal imaging-navigated synergistic therapies

Abstract Multimodal phototheranostics has been recognized as one of the most momentous advances in cancer treatment. Of particular interest is a single molecular species simultaneously featuring by multiple imaging and synergistic phototherapies, and the development of such molecular species is nevertheless a formidably challenging task. Herein, we innovatively designed and synthesized three aggregation-induced emission (AIE)-active molecules with emission in the second near-infrared (NIR-II) window, by employing 10H-indeno[1,2-b][1,2,5]thiadiazolo[3,4-g]quinoxalin-10-one as the electron acceptor, 4-(tert-butyl)-N-(4-(tert-butyl)phenyl)-N-phenylaniline as the electron donor, and different π-bridge moieties. One of those molecules, namely OTTITQ, is capable of afford long absorption and emission wavelengths, efficient type I reactive oxygen species (ROS) generation, and high photothermal conversion efficiency. Quantum chemical calculations and molecular dynamics simulations substantiated the structure-activity relationship of the molecules, the excited-state energy dissipation pathways, and the impact of intramolecular motions on photophysical properties, while elucidating the mechanism of the AIE phenomenon. Moreover, OTTITQ nanoparticles (NPs) offer unprecedented performance on fluorescence-photoacoustic-photothermal trimodal imaging navigated photodynamic-photothermal synergistic therapies for bladder cancer.