Early Diagnosis of Liver Injury and Real-Time Evaluation of Photothermal Therapy Efficacy with a Viscosity-Responsive NIR-II Smart Molecule.

The early diagnosis of liver injury and in situ real-time monitoring of tumor therapy efficacy are important for the enhancement of personalized precision therapy but remain challenging due to the lack of reliable in vivo visualization tools with integrated diagnostic, therapeutic, and efficacy monitoring functions. Herein, a smart second near-infrared window (NIR-II) molecule (BITX-OH) is rationally designed for diagnosis and therapy by vinyl-bridging hydroxyl diphenyl xanthine unit and benzo[cd]indolium skeleton. BITX-OH exhibits high selectivity and sensitivity toward viscosity, exhibiting a significant enhancement (1167-fold) in NIR-II fluorescence at 962 nm. With the assistance of BITX-OH and NIR-II fluorescence imaging, early diagnosis and therapeutic evaluation of non-alcoholic fatty liver (NAFL), as well as in-site real-time monitoring of hepatic fibrosis (HF) in live mice have been successfully achieved, which is at least several hours earlier than the typical clinical test. Notably, BITX-OH displays excellent photothermal conversion efficiency when exposed to an 808 nm laser, which can induce tumor ablation and increase viscosity, thereby enhancing NIR-II fluorescence for the real-time evaluation of photothermal therapy (PTT). This viscosity-based "self-monitoring" strategy provides a convenient and reliable platform for timely obtaining therapeutic feedback to avoid over- or under-treatment, thus enabling personalized precision therapy.