A near-infrared fluorescent probe based on Au3+/Pd2+ complexes for glutathione sensing: Applications in acute liver injury, hepatocellular carcinoma, and ferroptosis exploration

Liver diseases, particularly acute alcoholic liver injury (AALI), drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC), have become global public health issues. Glutathione (GSH), as an important antioxidant, plays a crucial role in the liver, and its changes are closely associated with liver injury and the development of liver cancer. Therefore, accurately monitoring GSH variations is critical for understanding liver injury mechanisms, early diagnosis, and treatment evaluation. However, traditional detection methods suffer from insufficient sensitivity and selectivity. To address these challenges, we developed an innovative DR-Au³⁺/DR-Pd²⁺ complex probe that can rapidly and sensitively detect GSH through near-infrared (NIR) fluorescence changes. This probe, with the optimal excitation and emission wavelengths of the probe both located in the NIR region, exhibits excellent selectivity and liver-targeting ability, overcoming the imprecision localization problems of traditional methods. In the AALI and DILI models, the optimized DR-Au³⁺ probe enables real-time monitoring of GSH level fluctuations, providing a powerful tool for early diagnosis of liver injury and dynamic evaluation of therapeutic efficacy. In the DILI and HCC models, the DR-Au³⁺ probe enables visualization and quantitative monitoring of the ferroptosis process, offering new perspectives and approaches for targeted therapy research. The DR-Au³⁺ probe we developed pioneers innovative strategies for establishing accurate diagnostic protocols and individualized therapeutic regimens in hepatic injury and hepatocellular carcinoma management.