One-step detection of circulating tumor cells in ovarian cancer using enhanced fluorescent silica nanoparticles

Int J Nanomedicine. 2013:8:2247-57. doi: 10.2147/IJN.S45059. Epub 2013 Jun 21.

Abstract

Ovarian cancer is the fifth-leading cause of cancer-related deaths among women as a result of late diagnosis. For survival rates to improve, more sensitive and specific methods for earlier detection of ovarian cancer are needed. This study presents the development of rapid and specific one-step circulating tumor cell (CTC) detection using flow cytometry in a whole-blood sample with fluorescent silica nanoparticles. We prepared magnetic nanoparticle (MNP)-SiO2(rhodamine B isothiocyanate [RITC]) (MNP-SiO2[RITC] incorporating organic dyes [RITC, ëmax(ex/em) = 543/580 nm]) in the silica shell. We then controlled the amount of organic dye in the silica shell of MNP-SiO2(RITC) for increased fluorescence intensity to overcome the autofluorescence of whole blood and increase the sensitivity of CTC detection in whole blood. Next, we modified the surface function group of MNP-SiO2(RITC) from -OH to polyethylene glycol (PEG)/COOH and conjugated a mucin 1 cell surface-associated (MUC1) antibody on the surface of MNP-SiO2(RITC) for CTC detection. To study the specific targeting efficiency of MUC1-MNP-SiO2(RITC), we used immunocytochemistry with a MUC1-positive human ovarian cancer cell line and a negative human embryonic kidney cell line. This technology was capable of detecting 100 ovarian cancer cells in 50 μL of whole blood. In conclusion, we developed a one-step CTC detection technology in ovarian cancer based on multifunctional silica nanoparticles and the use of flow cytometry.

Keywords: CTCs; MUC1; circulating tumor cells; fluorescent nanoprobe; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / metabolism
  • Cell Line, Tumor
  • Female
  • Flow Cytometry
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / pharmacokinetics
  • HEK293 Cells
  • Humans
  • Microscopy, Fluorescence
  • Mucin-1 / immunology
  • Mucin-1 / metabolism
  • Nanoparticles / chemistry*
  • Neoplastic Cells, Circulating* / chemistry
  • Neoplastic Cells, Circulating* / metabolism
  • Ovarian Neoplasms / metabolism*
  • Silicon Dioxide / chemistry*
  • Silicon Dioxide / pharmacokinetics
  • Spectrophotometry, Ultraviolet

Substances

  • Antibodies, Monoclonal
  • Fluorescent Dyes
  • MUC1 protein, human
  • Mucin-1
  • Silicon Dioxide