In Vivo Coinstantaneous Identification of Hepatocellular Carcinoma Circulating Tumor Cells by Dual-Targeting Magnetic-Fluorescent Nanobeads.

Abstract

Circulating tumor cells (CTCs) have been considered as a potential biomarker for evaluation of cancer metastasis and prognosis, especially in hepatocellular carcinoma (HCC). However, the isolation and detection of rare CTCs in HCC patients face enormous challenges due to omittance and nonspecific binding. We previously designed a small molecular NIR fluoresent agent, named MLP, which had high affinity with a tumor cell-overexpressed enzyme, aminopeptidase N (APN). Based on that, in this work we introduced a novel strategy via coassembling the antiepithelial cell adhesion molecule (EpCAM) antibody and MLPinto theFe3O4 magnetic nanobeads (MB-MLP-EpCAM) to isolate and identify HCC-CTCs coinstantaneously. MB-MLP-EpCAM significantly improved the CTC-capture efficiency (>85%) without sacrificing cell viability (>90%). Most importantly, the advantages of precise dual-targetability, high resolution of fluorescence imaging, and prominent selectivity make our nanoplatform have great potential to achieve in vivo real-time identification and monitoring of CTCs clinically.