A near-infrared viscosity probe for dynamic imaging of multilevel drug-induced liver injury.

Drug-induced liver injury (DILI) disrupts hepatocellular homeostasis during the early phase. However, conventional detection methods often only become apparent after the injury has advanced. Cellular viscosity is a characteristic of the intracellular microenvironment, which regulates diffusion, membrane fluidity, organelle transport, and signaling, and can change rapidly under stress. As DILI can elicit mitochondrial dysfunction, endoplasmic reticulum stress, and lipid droplet remodeling, localized viscosity changes emerge early in the injury process. Here we report a near-infrared viscosity probe named WZY-1 based on a pyridinium-aryl molecular rotor. In high-viscosity media, the restriction of intramolecular rotation suppresses the twisted intramolecular charge transfer (TICT) and enhances the emission intensity. WZY-1 provides long-wavelength near-infrared emission with a large Stokes shift, maintains stable signals, shows tolerance to common ions and reactive species, and displays good biocompatibility. At the cellular level, WZY-1 can distinguish hepatocellular carcinoma cells from normal hepatic cells, and detect endogenous viscosity changes. In DILI models, it visualizes viscosity changes in cells, tissue, and live mice. Taken together, WZY-1 enables noninvasive, in situ, real-time readout of viscosity and supports early assessment of DILI across cellular, tissue, and animal levels.