Microviscosity-Gated Excited-State Partitioning in a NIR-II Molecular Rotor for Disease Imaging and Imaging-Guided Photothermal Therapy

Microviscosity is an underexploited pathological cue that can be harnessed to regulate excited-state energy dissipation in organic near-infrared II (NIR-II, 1000-1700 nm) fluorophores. Here we introduce a twisted intramolecular charge transfer molecular rotor that uses microviscosity to gate radiative versus nonradiative decay, delivering a fluorescence “off” state in low-viscosity environments and a weak-but-sufficient NIR-II fluorescence turn-on in viscosity-elevated pathology while keeping nonradiative dissipation dominant for photothermal heating. A tunable donor-π-acceptor library was synthesized to drive absorption/emission toward the NIR-II window and calibrate a “dim-but-hot” photophysical profile. Molecularly dispersed FMR-1105-PEG enables in vivo NIR-II imaging in nonalcoholic fatty liver disease and acetaminophen-induced liver injury models. For tumor translation, micellization retains a measurable viscosity dependence (Förster-Hoffmann-type) while markedly increasing the apparent molar extinction coefficient, thereby enabling efficient 1064 nm photothermal activation, immunogenic cell death hallmarks in vitro , and imaging-guided tumor ablation even under tissue coverage, with favorable biosafety.