Dual‐Targeting Peptide Assembly Probe for Precise Detection of Biomarkers of Circulating Tumor Cells in Hepatocellular Carcinoma

Abstract Hepatocellular carcinoma (HCC) represents the predominant malignant hepatic neoplasm globally and constitutes a principal contributor to cancer‐associated mortality. Contemporary diagnostic methodologies exhibit limited sensitivity for early‐stage detection, while the disease's substantial metastatic propensity and recurrence rates significantly compromise survival outcomes. Circulating tumor cells (CTCs), detectable throughout disease progression and harboring crucial pathological signatures, present compelling potential as liquid biopsy biomarkers for early‐stage detection and prognostic assessment. However, the inherently sparse distribution of CTCs in HCC patients, coupled with the complex technical requirements and substantial economic burden of existing detection platforms, presents significant impediments to analytical precision and broad clinical implementation. Here, the development of an innovative dual‐targeting peptide assembly system incorporating the HCC‐specific peptide P47 (SQDIRTWNGTRS) and the N‐cadherin receptor‐targeting peptide NP (NSATRYKC) is reported. Upon self‐assembly, this molecular system generates nanofibers exhibiting high‐density recognition domains, facilitating enhanced sensitivity and superior signal‐to‐noise ratio in fluorescence‐based HCC‐CTCs detection through a simplified methodological approach. The experimental findings demonstrate robust CTCs detection capability in 1 mL blood specimens across diverse patient demographics and disease stages, establishing a cost‐effective liquid biopsy platform. This novel approach provides valuable insights for precision medicine applications, offering significant implications for early‐stage diagnosis and prognostic evaluation of HCC.