Simple monitoring of cancer cells using nanoparticles.

Here we present a new strategy for a simple and fast detection of cancer circulating cells (CTCs) using nanoparticles. The human colon adenocarcinoma cell line (Caco2) was chosen as a model CTC. Similarly to other adenocarcinomas, colon adenocarcinoma cells have a strong expression of EpCAM, and for this reason this glycoprotein was used as the capture target. We combine the capturing capability of anti-EpCAM functionalized magnetic beads (MBs) and the specific labeling through antibody-modified gold nanoparticles (AuNPs), with the sensitivity of the AuNPs-electrocatalyzed hydrogen evolution reaction (HER) detection technique. The fully optimized process was used for the electrochemical detection of Caco2 cells in the presence of monocytes (THP-1), other circulating cells that could interfere in real blood samples. Therefore we obtained a novel and simple in situ-like sensing format that we applied for the rapid quantification of AuNPs-labeled CTCs in the presence of other human cells.

[1]  H. Mellstedt,et al.  Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. , 2012, Cancer treatment reviews.

[2]  Arben Merkoçi,et al.  Gold nanoparticle-based electrochemical magnetoimmunosensor for rapid detection of anti-hepatitis B virus antibodies in human serum. , 2010, Biosensors & bioelectronics.

[3]  J L Nation,et al.  A new method using hexamethyldisilazane for preparation of soft insect tissues for scanning electron microscopy. , 1983, Stain technology.

[4]  Maciej Zborowski,et al.  Magnetic cell separation: characterization of magnetophoretic mobility. , 2003, Analytical chemistry.

[5]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[6]  M. Harmsen,et al.  Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule. , 2007, The American journal of pathology.

[7]  Brigitte Rack,et al.  Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Metastatic Breast Cancer: A Validation Study of the CellSearch System , 2007, Clinical Cancer Research.

[8]  J Loureiro,et al.  Magnetoresistive chip cytometer. , 2011, Lab on a chip.

[9]  Kai Li,et al.  Conjugated polymer loaded nanospheres with surface functionalization for simultaneous discrimination of different live cancer cells under single wavelength excitation. , 2011, Analytical chemistry.

[10]  J. Guillemot,et al.  Ep-CAM transfection in thymic epithelial cell lines triggers the formation of dynamic actin-rich protrusions involved in the organization of epithelial cell layers , 2001, Histochemistry and Cell Biology.

[11]  R. Christopherson,et al.  Cell Surface Markers in Colorectal Cancer Prognosis , 2010, International journal of molecular sciences.

[12]  Arben Merkoçi,et al.  Rapid identification and quantification of tumor cells using an electrocatalytic method based on gold nanoparticles. , 2009, Analytical chemistry.

[13]  Maëlle Perfézou,et al.  Cancer detection using nanoparticle-based sensors. , 2012, Chemical Society reviews.

[14]  Hong Wu,et al.  Three-dimensional nanostructured substrates toward efficient capture of circulating tumor cells. , 2009, Angewandte Chemie.

[15]  Sabine Riethdorf,et al.  Review: Biological relevance of disseminated tumor cells in cancer patients , 2008, International journal of cancer.

[16]  Alessandro Lugli,et al.  Frequent EpCam protein expression in human carcinomas. , 2004, Human pathology.

[17]  L. Weiner,et al.  Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer. , 2006, Clinical colorectal cancer.

[18]  B. Topal,et al.  Quantitative RT-PCR detection of colorectal tumor cells in peripheral blood--a systematic review. , 2008, The Journal of surgical research.

[19]  Jonathan W. Uhr,et al.  Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases , 2004, Clinical Cancer Research.

[20]  Arben Merkoçi,et al.  Electrochemical detection of proteins using nanoparticles: applications to diagnostics. , 2010, Expert opinion on medical diagnostics.

[21]  K. Jensen,et al.  Cells on chips , 2006, Nature.

[22]  Arben Merkoçi,et al.  Enhanced gold nanoparticle based ELISA for a breast cancer biomarker. , 2010, Analytical chemistry.

[23]  Alfredo de la Escosura-Muñiz,et al.  Electrochemical quantification of gold nanoparticles based on their catalytic properties toward hydrogen formation: Application in magnetoimmunoassays , 2010 .

[24]  A S Perelson,et al.  Steric effects on multivalent ligand-receptor binding: exclusion of ligand sites by bound cell surface receptors. , 1999, Biophysical journal.

[25]  Klaus Pantel,et al.  Circulating tumour cells in cancer patients: challenges and perspectives. , 2010, Trends in molecular medicine.

[26]  G. Whitesides.  The origins and the future of microfluidics , 2006, Nature.

[27]  Martin Pumera,et al.  Magnetically trigged direct electrochemical detection of DNA hybridization using Au67 quantum dot as electrical tracer. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[28]  Jaap M. J. den Toonder,et al.  Circulating tumor cells: the Grand Challenge. , 2011, Lab on a chip.

[29]  K. Pantel,et al.  Clinical relevance and biology of circulating tumor cells , 2011, Breast Cancer Research.

[30]  M. Sanner,et al.  A dynamical study of antibody–antigen encounter reactions , 2007, Physical biology.

[31]  J. Bagu,et al.  Comparison of hexamethyldisilazane (HMDS), Peldri II, and critical‐point drying methods for scanning electron microscopy of biological specimens , 1993, Microscopy research and technique.

[32]  O. Gires,et al.  EpCAM (CD326) finding its role in cancer , 2007, British Journal of Cancer.

[33]  J. Hillier,et al.  The Formation of Colloidal Gold , 1953 .

[34]  C Hollmann,et al.  DETECTION OF DISSEMINATED TUMOR CELLS IN PERIPHERAL BLOOD , 2005, Critical reviews in clinical laboratory sciences.

[35]  Y. Kim,et al.  Subcellular distribution, synthesis, and release of carcinoembryonic antigen in cultured human colon adenocarcinoma cell lines. , 1983, Cancer research.

[36]  Arben Merkoçi,et al.  Double-codified gold nanolabels for enhanced immunoanalysis. , 2007, Analytical chemistry.

[37]  A. Giuliano,et al.  Detection of occult metastatic breast cancer cells in blood by a multimolecular marker assay: correlation with clinical stage of disease. , 2001, Cancer research.