Versatile Immunomagnetic Nanocarrier Platform for Capturing Cancer Cells

Abstract

Sensitive and quantitative assessment of changes in circulating tumor cells (CTCs) can help in cancer prognosis and in the evaluation of therapeutics efficacy. However, extremely low occurrence of CTCs in the peripheral blood (approximately one CTC per billion blood cells) and potential changes in molecular biomarkers during the process of epithelial to mesenchymal transition (EMT) create technical hurdles to the enrichment and enumeration CTCs. Recently, efforts have been directed toward development of antibody-capture assays based on the expression of the common biomarker - the epithelial cell adhesion molecule (EpCAM) of epithelium-derived cancer cells. Despite some promising results, the assays relying on EpCAM capture have shown inconsistent sensitivity in clinical settings and often fail to detect CTCs in patients with metastatic cancer. We have addressed this problem by the development of an assay based on hybrid magnetic/plasmonic nanocarriers and a microfluidic channel. In this assay cancer cells are specifically targeted by antibody-conjugated magnetic nanocarriers and are separated from normal blood cells by a magnetic force in a microfluidic chamber. Subsequently, immunofluorescence staining is used to differentiate CTCs from normal blood cells. We demonstrated in cell models of colon, breast and skin cancers that this platform can be easily adapted to a variety of biomarkers, targeting both surface receptor molecules and intracellular biomarkers of epithelial-derived cancer cells. Experiments in whole blood showed capture efficiency greater than 90% when two cancer biomarkers are used for cell capture. Thus, the combination of immunotargeted magnetic nanocarriers with microfluidics provides an important platform that can improve the effectiveness of current CTC assays by overcoming the problem of heterogeneity of tumor cells in the circulation.

A Facile and Green Synthetic Route for Preparation of Heterostructure Fe3O4@Au Nanocomposites

“…Figure 3 [16]. The maximum magnetization value of the core/shell magnetic NPs was around 10-20 emu/g at room temperature [19]. The direct coating of Au onto magnetic NPs severely decreased the saturation magnetizationof the magnetic core by 78% or more.…”

Rational Design of Materials Interface for Efficient Capture of Circulating Tumor Cells

“…By combing the immunomagnetic separation strategy and microfluidic technique, Immunomagnetic‐based microfluidic systems have also been developed for efficient CTCs capture and isolation 69, 70, 71, 72, 73, 74, 75, 76. Hoshino et al developed an immunomagnetic‐based microfluidic device for CTCs capture 69.…”

Microfluidic bio-particle manipulation for biotechnology

“…The third group focuses on the immunomagnetic bio-particle manipulation for selection of rare cells such as separation of tumor cells from other cell types such as blood cells. Using immunomagnetic labeling of the cancer cells, colon, skin and breast cancer cells have been successfully separated from whole blood [143]. Moreover, the separation of MCF-7, SK-BR-3 breast cancer cell lines from whole blood [48,99,64], capturing of rare colon and breast cancer cells with a very low concentration (10 9 : 1) [64], detection and concentration of influenza virus [98], the separation of tagged leukocytes in blood from RBCs with the use of magnetic stripes [144], collection of CD34+ stem cells from leukapheresis product [70,71] using millimeter size tube and a quadrupole magnet arrangement have been successfully performed.…”