“…Fluorescence imaging in the near-infrared region (NIR-I: 700–900 nm, NIR-II: 1000–1700 nm) has great potential for improving disease diagnosis due to its high sensitivity, good spatiotemporal resolution, and noninvasive visualization, especially in the NIR-II window, providing higher spatial resolution and deeper in vivo tissue penetration because of reduced photon scattering and autofluorescence. − Hence, smart activatable NIR fluorescent probes that can respond to biomarkers and cellular microenvironment are promising for early and accurate diagnosis of NAFLD and metastatic intestinal cancer. − As an important microenvironmental parameter, intracellular viscosity plays a crucial role in signal transduction, biological species diffusion, and cell metabolism. , Nevertheless, abnormal changes in viscosity in cells are closely related to different diseases, such as atherosclerosis, diabetes, and Alzheimer’s disease. , Moreover, cytoplasmic viscosity increase is also an essential physiological feature of NAFLD. , Viscosity-responsive fluorophores with a molecular rotor have been recently reported to monitor intracellular viscosity variations. − Unfortunately, because of the short emission wavelength and high background fluorescence, these fluorescent probes were mainly applied in monitoring viscosity in live cells, and there was no viscosity-responsive NIR-II fluorophore for early detection of NAFLD in living animals. On the other hand, low extracellular pH (6.5–6.8) is a cancer hallmark that plays an important role in tumor proliferation, invasion, and metastasis .…”