Water-Soluble Viscosity-Activated Molecular Rotor for In Situ Imaging of Liver Damage in the NIR-II Window

Microviscosity in the hepatic microenvironment changes during steatosis, matrix remodeling, and drug-induced injury but remains challenging to monitor in vivo. Here, we report JMR-1002-PEG, a water-soluble near-infrared II (NIR-II, 1000-1700 nm) fluorescent molecular rotor for viscosity-responsive liver imaging. The design of JMR-1002-PEG hinges on the strategic optimization of the donor-π-acceptor structure, where achieving NIR-II emission required careful modulation of the conjugated system while maintaining sufficient flexibility for viscosity-sensitive behavior. In mice, the probe reports hepatic microviscosity changes in acetaminophen-induced acute injury, CCl₄-induced fibrosis, and diet/drug-induced steatosis. Signal changes correlate with standard biochemical and histological markers and decrease after treatment. These findings identify PEGylated NIR-II molecular rotors as promising tools for noninvasive, real-time mechanism-based assessment of liver disease.