Dual-Selective and Dual-Enhanced SERS Nanoprobes Strategy for Circulating Hepatocellular Carcinoma Cells Detection

The detection of hepatocellular carcinoma (HCC) circulating tumor cells (CTCs) from a blood sample can be a very powerful noninvasive approach for the early detection and therapy of liver cancer. However, the extreme rarity of tumor cells in blood containing billions of other cells makes the capture and identification of CTCs with sufficient sensitivity and specificity a real challenge. Here, a magnetically assisted surface-enhanced Raman scattering (SERS) biosensor for HCC CTC detection is reported for the first time. The biosensor consists of two basic elements: anti-ASGPR antibody-Fe₃O₄@Ag magnetic nanoparticles and anti-GPC3 antibody-Au@Ag@DTNB nanorods. According to the dual-selectivity of the anti-ASGPR and anti-GPC3 antibodies and the dual-enhancement SERS signal of the MNPs silver shell and the Au@Ag NRs SERS tags, a limit of detection of 1 cell mL⁻¹ for HCC CTC in human peripheral blood samples with a linear relationship from 1 to 100 cells mL⁻¹ can be obtained. The system shows good performance in real serum, which suggests it may be a promising tool for HCC clinical diagnosis.