Near-Infrared Fluorescent Probe for Simultaneously Imaging Ferrous Ions and Viscosity in a Mouse Model of Hepatocellular Carcinoma

Abnormal ferrous ion (Fe²⁺) levels lead to an increase in reactive oxygen species (ROS) in cells, disrupting intracellular viscosity and the occurrence of hepatocellular carcinoma (HCC). Simultaneously visualizing Fe²⁺ and intracellular viscosity is essential for understanding the detailed pathophysiological processes of HCC. Herein, we report the first dual-responsive probe, QM-FV, capable of simultaneously monitoring Fe²⁺ and viscosity. QM-FV shows highly selective turn-on near-infrared fluorescence (∼30-fold enhancement at 740 nm) for Fe²⁺ with high sensitivity (LOD = 25 nM) and a significant Stokes shift (290 nm). Moreover, QM-FV shows a distinct orange-red fluorescence enhancement at 587 nm as the viscosity increases. Due to its lower cytotoxicity and high sensitivity, QM-FV can distinguish cancer cells from normal cells by detecting Fe²⁺ and viscosity in dual channels. More importantly, using QM-FV, we found that the levels of Fe²⁺ and viscosity elevated in the precancerous stage of HCC and gradually increased as the disease progressed. Overall, this work provides a new potential tool for investigating viscosity and Fe²⁺-related pathological processes underlying HCC.