Monitoring hepatic cysteine dynamics in obesity models with sulfur-substituted hemicyanine-based nanoprobes

Cysteine (Cys) plays pivotal roles in redox homeostasis and metabolic regulation, with its dysregulation implicated in obesity-related hepatic disorders. Here, we developed a sulfur-substituted hemicyanine-based nanoprobe (Cys-NP) for photoacoustic imaging of hepatic Cys dynamics. The Cys-responsive molecular probe (Cys-MP) was encapsulated in mPEG-DSPE nanoparticles to overcome aqueous solubility limitations, yielding monodisperse nanoparticles with an average diameter of 28.7 nm and excellent colloidal stability. Sulfur substitution endowed the probe enhanced photoacoustic signals compared to oxygenated analogs, while selective Cys recognition triggered a bathochromic shift and yielded a detection limit of 0.13 μM. In high-fat-diet-induced obese mice, Cys-NP revealed significantly elevated hepatic Cys levels correlating with histopathological steatosis and hypercholesterolemia. This work establishes a nanotechnology-enabled strategy for mapping redox metabolism in metabolic diseases, offering both mechanistic insights and diagnostic potential.