Conformational restriction-engineered near-infrared fluorescent probe for tracking viscosity dynamics during ferroptosis in sepsis.

Sepsis is a life-threatening inflammatory response to infection and is increasingly linked to dysregulated iron metabolism and ferroptosis. Monitoring the viscosity dynamics during ferroptosis is crucial for understanding sepsis progression. This work presents a novel near-infrared fluorescent probe ROBN for highly selective and sensitive detection of microenvironmental viscosity. Due to the conformational restrictions imposed by the rigid plane formed by the julolidine group, ROBN is regulated by the twisted intramolecular charge transfer (TICT) mechanism and exhibits a significant 44-fold fluorescence increase in high-viscosity environments. This probe exhibits low cytotoxicity and could effectively monitor viscosity changes in various cell lines, especially in mitochondria. Furthermore, ROBN enabled the visualization of elevated viscosity associated with ferroptosis in the inflammatory model of cells and zebrafish induced by LPS. Importantly, it was successfully employed in monitoring sepsis progression and organ-specific viscosity changes in the mouse sepsis model. This probe provides a powerful tool for real-time tracking of viscosity alterations during sepsis and offers valuable insights into ferroptosis mechanisms and potential diagnostic strategies for sepsis.