AIE-active dual-channel fluorescent probe for simultaneous viscosity and HClO detection in ferroptosis, acute liver injury and hepatocellular carcinoma models

This study addresses the technical challenge of simultaneously detecting viscosity and hypochlorous acid (HClO) within the liver disease microenvironment by developing a novel near-infrared (NIR) dual-channel fluorescence probe, BCz-DCN-TPA, based on the aggregation-induced emission (AIE) mechanism. The probe exhibits pronounced fluorescence enhancement at 675 nm (viscosity-responsive) and 465 nm (HClO-responsive), attributed to the restriction of intramolecular motion (RIM) effect and HClO-specific oxidation reactions, respectively. It also possesses high sensitivity, excellent selectivity (toward 15 types of interferents), superior photostability (for more than 300 min), and a low limit of detection (LOD) as low as 0.233 nM for HClO. Theoretical calculations revealed the ground state and excited state reaction pathways underlying the reaction between HClO and BCz-DCN-TPA. In vitro experiments validated its ability to monitor real-time changes in viscosity and oxidative stress levels during ferroptosis, which auds in elucidating ferroptosis mechanisms. In acetaminophen (APAP)-induced acute liver injury (ALI) and hepatocellular carcinoma models, the probe tracked dual parameters abnormal viscosity and HClO levels in liver injury regions and tumor microenvironments in vivo, with live imaging clearly delineating lesion areas. Notably, BCz-DCN-TPA enabled deep tissue photoacoustic imaging (PAI) in a hepatocellular carcinoma model. This multimodal probe provides a versatile platform for studying liver disease pathology and advancing precision diagnosis and treatment strategies.