Application of a near-infrared viscosity-responsive fluorescent probe for lysosomal targeting in fatty liver mice.

Viscosity is a fundamental property in biological systems, influencing organelle function and molecular diffusion. Abnormal viscosity is associated with diseases such as metabolic disorders, neurodegeneration, and cancer. Lysosomes, central to cellular degradation and recycling, are sensitive to viscosity changes, which can disrupt enzymatic activity and cellular homeostasis. Monitoring lysosomal viscosity provides essential information on lysosomal health, helping to uncover underlying mechanisms in various diseases. Recognizing the need for effective monitoring of lysosomal viscosity changes in living cells, we have developed a near-infrared (NIR) viscosity-responsive fluorescent probe, VFLyso, specifically designed for lysosomal targeting. Based on the twisted intramolecular charge transfer (TICT) mechanism, VFLyso exhibits strong NIR fluorescence, a fast response, and a notable fluorescence response to viscosity variations (F/F = 65.5-fold), along with excellent selectivity and stability under physiological conditions. Our studies demonstrated that VFLyso could accurately monitor lysosomal viscosity changes in both cell cultures and animal models, including zebrafish and mouse models of fatty liver. This work not only provides a powerful tool for real-time monitoring of lysosomal viscosity but also offers valuable insights into the role of viscosity in disease progression, paving the way for potential diagnostic applications in related disorders.