Genetic immunotherapy for hepatocellular carcinoma by endothelial progenitor cells armed with cytosine deaminase

J Biomed Nanotechnol. 2014 Feb;10(2):271-7. doi: 10.1166/jbn.2014.1766.

Abstract

Endothelial progenitor cells (EPCs) serve as cellular vehicles for targeting cancer cells and are a powerful tool for delivery of therapeutic genes. Cytosine deaminase (CD), a kind of frequent suicide gene which can kill carcinoma cells by converting a non-poisonous pro-drug 5-flucytosine (5-FC) into a poisonous cytotoxic 5-fluorouracil (5-FU). We combined super-paramagnetic iron oxide (SPIO) nanoparticles labeled EPCs with CD gene to treat grafted liver carcinomas and tracked them with 7.0 T Magnetic resonance imaging (MRI). Results showed that the therapeutic EPCs loaded with CD plus 5-Fc provided stronger carcinoma growth suppression compared with treatment using CD alone. The CD/5-Fc significantly inhibited the growth of endothelial cells and induced carcinoma cells apoptosis. These results indicate that EPCs transfected with anti-carcinoma genes can be used in carcinoma therapy as a novel therapeutic modality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Proliferation
  • Cytosine Deaminase / genetics
  • Cytosine Deaminase / therapeutic use*
  • Dextrans / metabolism
  • Endothelial Cells / cytology*
  • Enzyme Assays
  • Ferrocyanides / metabolism
  • Fluorescence
  • Genetic Therapy*
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Immunotherapy*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles
  • Staining and Labeling
  • Stem Cells / cytology
  • Stem Cells / enzymology*

Substances

  • Dextrans
  • Ferrocyanides
  • Magnetite Nanoparticles
  • Cytosine Deaminase
  • ferumoxides
  • ferric ferrocyanide