Two-dimensional NIR-II AIE nanotheranostic probes with ultralarge Stokes shifts for surgical navigation and ablation of glioma

Near-infrared (NIR) fluorescence probes featuring ultralarge Stokes shifts and efficient aggregate-state luminescence are highly desirable for bioimaging yet remain scarce due to formidable synthetic challenges and intricate photophysical modulation. We report a facile one-step click reaction to synthesize a tetracyanoquinodimethane-derived NIR probe (TNQ2) that overcomes the long-standing nonfluorescence limitation while achieving an unprecedented 445-nanometer Stokes shift. TNQ2 self-assembles into the smallest-sized two-dimensional J-aggregates (sub-160 nanometers) with a red-shift absorption from 545 to 725 nanometers and aggregation-enhanced emission around 1000 nanometers. The radiative/nonradiative modulation balances the fluorescence/photothermal/photodynamic effect to support high-sensitivity NIR-II fluorescence imaging-guided precise glioma resection and postoperative phototherapy to substantially extend survival in orthotopic glioma models. Our molecule/nanoengineering strategy establishes a transformative paradigm for developing advanced NIR phototheranostics for brain diseases.