Advances in galactose-based small-molecule hepatocyte-targeting probes for detecting biomarkers in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a type of malignant tumor with a low early detection rate, high morbidity, and high mortality. Therefore, early diagnosis of HCC is essential for improving patient survival and treatment outcomes. Traditional diagnostic approaches generally exhibit insufficient specificity and sensitivity. However, small-molecule fluorescent probes offer advantages, such as non-invasiveness, high sensitivity, and real-time imaging capabilities, are considered ideal tools for liver cancer research, and are widely used in imaging and treatment studies. Asialoglycoprotein receptor (ASGPR) is overexpressed on hepatoma cells, and galactose can be recognized by ASGPR via the cluster glycoside effect; hence, various galactose-based small-molecule hepatocyte-targeting fluorescent probes have been developed. These probes can target hepatocytes via receptor-mediated endocytosis and release a fluorescent dye upon reactions with specific small molecules or enzymatic biomarkers, making them powerful tools for the early diagnosis of HCC. The present work is a review of recent advances in galactose-based small-molecule hepatocyte-targeting probes for detecting HCC-related markers and provides a detailed account of their physicochemical properties and applications in cellular and biological systems. We also conduct an in-depth examination of existing issues and provide a summary of the future trends and challenges. We hope that this review may promote the development of novel fluorescent probes for HCC detection and further provide meaningful guidance for the diagnosis and treatment of HCC.