Ethylenediamine functionalized-single-walled nanotube (f-SWNT)-assisted in vitro delivery of the oncogene suppressor p53 gene to breast cancer MCF-7 cells

Int J Nanomedicine. 2011:6:1045-55. doi: 10.2147/IJN.S17684. Epub 2011 May 18.

Abstract

A gene delivery concept based on ethylenediamine-functionalized single-walled carbon nanotubes (f-SWCNTs) using the oncogene suppressor p53 gene as a model gene was successfully tested in vitro in MCF-7 breast cancer cells. The f-SWCNTs-p53 complexes were introduced into the cell medium at a concentration of 20 μg mL(-1) and cells were exposed for 24, 48, and 72 hours. Standard ethidium bromide and acridine orange assays were used to detect apoptotic cells and indicated that a significantly larger percentage of the cells (approx 40%) were dead after 72 hours of exposure to f-SWCNTs-p53 as compared to the control cells, which were exposed to only p53 or f-SWCNTs, respectively. To further support the uptake and expression of the genes within the cells, green fluorescent protein-tagged p53, attached to the f-SWCNTs was added to the medium and the complex was observed to be strongly expressed in the cells. Moreover, caspase 3 activity was found to be highly enhanced in cells incubated with the f-SWCNTs-p53 complex, indicating strongly induced apoptosis. This system could be the foundation for novel gene delivery platforms based on the unique structural and morphological properties of multi-functional nanomaterials.

Keywords: cancer cells; carbon nanotubes; gene delivery; p53 oncogene suppressor.

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

  • Analysis of Variance
  • Apoptosis / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Ethylenediamines / chemistry*
  • Female
  • Genes, p53*
  • Genetic Therapy / methods*
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Humans
  • Microscopy, Atomic Force
  • Microscopy, Electron, Scanning
  • Nanotubes, Carbon / chemistry*
  • Nanotubes, Carbon / ultrastructure
  • Thermogravimetry

Substances

  • Ethylenediamines
  • Nanotubes, Carbon
  • Green Fluorescent Proteins
  • ethylenediamine
  • Caspase 3