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

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 10-indeno[1,2-][1,2,5]thiadiazolo[3,4-]quinoxalin-10-one as the electron acceptor, 4-(-butyl)--(4-(-butyl)phenyl)--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.