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 in multiple imaging and synergistic phototherapies; the development of such a 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 4,12-bis(7-(4-(bis(4-(tert-butyl)phenyl)amino)phenyl)-2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-10H-indeno[1,2-b][1,2,5]thiadiazolo[3,4-g]quinoxalin-10-one (OTTITQ), is capable of affording long absorption and emission wavelengths, efficient type I reactive oxygen species 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 offer unprecedented performance on fluorescence–photoacoustic–photothermal trimodal imaging-navigated photodynamic–photothermal synergistic therapies for bladder cancer.