Capture of Heterogeneous Circulating Tumor Cells in Colorectal Cancer Patients on an Immunomagnetic and Anti-Nonspecific Adsorption Platform.

Abstract

Circulating tumor cells (CTC) have been represented by different phenotypes due to the epithelial-mesenchymal transition (EMT), which are epithelial CTC (E-CTC), mesenchymal CTC (M-CTC), and mixed (epithelial, mesenchymal) CTC (EM-CTC). Limited work has systematically discussed the associations of CTC number, especially proportions of E-CTC, M-CTC, and EM-CTC in total CTC, with colorectal cancer (CRC) progressions via a simple method with high performances. To achieve this goal, this paper presents the fabrication of a novel anti-nonspecific adsorption immunomagnetic platform called Fe3O4@SiO2@PTMAO@Aptamer, which was obtained by modifying polymeric trimethylamine N-oxide (PTMAO) on magnetic Fe3O4@SiO2, which was then linked with dual aptamers of an epithelial cellular adhesion molecule (EpCAM) and cell surface vimentin (CSV), targeting different CTC phenotypes. Results demonstrated that the abundant coating of PTMAO on Fe3O4@SiO2 improved the anti-nonspecific adsorption and noncell adhesion abilities of the immunomagnetic particles and could capture heterogeneous CTC with higher efficiency within 10 min. These excellent performances of Fe3O4@SiO2@PTMAO@Aptamer allowed us to inspect the correlations of numbers of E-CTC, M-CTC, EM-CTC, or proportions of them in total CTC with clinical information on CRC patients in detail. Our data innovatively and clearly revealed that the captured CTC, especially M-CTC proportion, displayed more close associations with progression, diagnosis, surgery, and chemotherapeutic effects for CRC patients. Overall, we believe that our approach will bring a new understanding of CTC-based liquid biopsy for cancer diagnosis and treatment.