Versatile immunomagnetic nanocarrier platform for capturing cancer cells

Chun Hsien Wu, Yu Yen Huang, Peng Chen, Kazunori Hoshino, Huaying Liu, Eugene P. Frenkel, John X J Zhang, Konstantin V. Sokolov

Research output: Contribution to journalArticle

71 Citations (Scopus)

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 create technical hurdles to the enrichment and enumeration of 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.

Original languageEnglish (US)
Pages (from-to)8816-8823
Number of pages8
JournalACS Nano
Volume7
Issue number10
DOIs
StatePublished - Oct 22 2013

Fingerprint

Tumors
tumors
platforms
cancer
Cells
biomarkers
Biomarkers
Assays
Blood
blood cells
Microfluidics
Cell adhesion
Cell Adhesion Molecules
cells
antibodies
Antibodies
Molecules
blood
adhesion
molecules

Keywords

  • circulating tumor cells
  • gold shell/magnetic core nanoparticles
  • immunomagnetic assay
  • microfluidic chip

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

Cite this

Wu, C. H., Huang, Y. Y., Chen, P., Hoshino, K., Liu, H., Frenkel, E. P., ... Sokolov, K. V. (2013). Versatile immunomagnetic nanocarrier platform for capturing cancer cells. ACS Nano, 7(10), 8816-8823. https://doi.org/10.1021/nn403281e

Versatile immunomagnetic nanocarrier platform for capturing cancer cells. / Wu, Chun Hsien; Huang, Yu Yen; Chen, Peng; Hoshino, Kazunori; Liu, Huaying; Frenkel, Eugene P.; Zhang, John X J; Sokolov, Konstantin V.

In: ACS Nano, Vol. 7, No. 10, 22.10.2013, p. 8816-8823.

Research output: Contribution to journalArticle

Wu, CH, Huang, YY, Chen, P, Hoshino, K, Liu, H, Frenkel, EP, Zhang, JXJ & Sokolov, KV 2013, 'Versatile immunomagnetic nanocarrier platform for capturing cancer cells', ACS Nano, vol. 7, no. 10, pp. 8816-8823. https://doi.org/10.1021/nn403281e
Wu, Chun Hsien ; Huang, Yu Yen ; Chen, Peng ; Hoshino, Kazunori ; Liu, Huaying ; Frenkel, Eugene P. ; Zhang, John X J ; Sokolov, Konstantin V. / Versatile immunomagnetic nanocarrier platform for capturing cancer cells. In: ACS Nano. 2013 ; Vol. 7, No. 10. pp. 8816-8823.
@article{e5e85e5248e14fceb8f2109b28b1cfe8,
title = "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 create technical hurdles to the enrichment and enumeration of 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.",
keywords = "circulating tumor cells, gold shell/magnetic core nanoparticles, immunomagnetic assay, microfluidic chip",
author = "Wu, {Chun Hsien} and Huang, {Yu Yen} and Peng Chen and Kazunori Hoshino and Huaying Liu and Frenkel, {Eugene P.} and Zhang, {John X J} and Sokolov, {Konstantin V.}",
year = "2013",
month = "10",
day = "22",
doi = "10.1021/nn403281e",
language = "English (US)",
volume = "7",
pages = "8816--8823",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "10",

}

TY - JOUR

T1 - Versatile immunomagnetic nanocarrier platform for capturing cancer cells

AU - Wu, Chun Hsien

AU - Huang, Yu Yen

AU - Chen, Peng

AU - Hoshino, Kazunori

AU - Liu, Huaying

AU - Frenkel, Eugene P.

AU - Zhang, John X J

AU - Sokolov, Konstantin V.

PY - 2013/10/22

Y1 - 2013/10/22

N2 - 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 create technical hurdles to the enrichment and enumeration of 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.

AB - 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 create technical hurdles to the enrichment and enumeration of 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.

KW - circulating tumor cells

KW - gold shell/magnetic core nanoparticles

KW - immunomagnetic assay

KW - microfluidic chip

UR - http://www.scopus.com/inward/record.url?scp=84887005212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887005212&partnerID=8YFLogxK

U2 - 10.1021/nn403281e

DO - 10.1021/nn403281e

M3 - Article

VL - 7

SP - 8816

EP - 8823

JO - ACS Nano

JF - ACS Nano

SN - 1936-0851

IS - 10

ER -