NanoFlares for the detection, isolation, and culture of live tumor cells from human blood

Proc Natl Acad Sci U S A. 2014 Dec 2;111(48):17104-9. doi: 10.1073/pnas.1418637111. Epub 2014 Nov 17.

Abstract

Metastasis portends a poor prognosis for cancer patients. Primary tumor cells disseminate through the bloodstream before the appearance of detectable metastatic lesions. The analysis of cancer cells in blood—so-called circulating tumor cells (CTCs)—may provide unprecedented opportunities for metastatic risk assessment and investigation. NanoFlares are nanoconstructs that enable live-cell detection of intracellular mRNA. NanoFlares, when coupled with flow cytometry, can be used to fluorescently detect genetic markers of CTCs in the context of whole blood. They allow one to detect as few as 100 live cancer cells per mL of blood and subsequently culture those cells. This technique can also be used to detect CTCs in a murine model of metastatic breast cancer. As such, NanoFlares provide, to our knowledge, the first genetic-based approach for detecting, isolating, and characterizing live cancer cells from blood and may provide new opportunities for cancer diagnosis, prognosis, and personalized therapy.

Keywords: NanoFlares; cancer metastasis; diagnostic; mRNA; nanotechnology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carbocyanines / chemistry*
  • Carbocyanines / metabolism
  • Cell Line, Tumor
  • DNA, Antisense / chemistry*
  • DNA, Antisense / genetics
  • DNA, Antisense / metabolism
  • Female
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Gold / chemistry*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Metal Nanoparticles / chemistry*
  • Microscopy, Fluorescence
  • Nanotechnology / methods
  • Neoplastic Cells, Circulating / chemistry*
  • Neoplastic Cells, Circulating / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Red Fluorescent Protein
  • Transplantation, Heterologous
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • Biomarkers, Tumor
  • Cadherins
  • Carbocyanines
  • DNA, Antisense
  • Fibronectins
  • Luminescent Proteins
  • RNA, Messenger
  • Vimentin
  • cyanine dye 5
  • Green Fluorescent Proteins
  • Gold