Illuminating liver fibrosis: recent progress in the design and applications of highly sensitive fluorescent probes

Liver fibrosis involves excessive, disorganized extracellular matrix deposition in the liver, critically driving progression from chronic liver disease to cirrhosis and determining patient prognosis. Although histological examination of liver tissue biopsies continues to serve as the most reliable diagnostic approach, the development of precise detection methods remains crucial for enabling timely therapeutic interventions and improving patient management. Recent advances in fluorescent probes have transformed the detection of liver fibrosis, enabling real-time, non-invasive visualization of biomarkers and microenvironmental changes. Based on its design strategy, targeted objects and functional characteristics, this review systematically classifies state-of-the-art fluorescent probes into five categories: probes directly targeting liver fibrosis markers, enzyme-activated probes, microenvironment-responsive probes, intracellular targeting probes, and multifunctional theranostic probes. Among them, near-infrared II (NIR-II, 1000-1700 nm) imaging and genetically encoded probes boost molecular precision and resolution, yet clinical application faces challenges from limited tissue penetration and poor biocompatibility. Consequently, future research in this field will concentrate on the development of NIR II probes, the discovery of biomarkers in biofluids, and the design of new therapeutic interventions. By elucidating design principles and applications, this review aims to bridge the gap between molecular innovation and clinical practice, ultimately advancing precision medicine for liver fibrosis.