Gene delivery into human cancer cells by cationic lipid-mediated magnetofection

Int J Pharm. 2013 Mar 25;446(1-2):87-99. doi: 10.1016/j.ijpharm.2013.01.055. Epub 2013 Feb 13.

Abstract

In this study, a combination of magnetic nanoparticles (MNPs) together with cationic lipid N,N-di-n-hexadecyl-N,N-dihydroxyethylammonium chloride formulated with colipid cholesterol, upon magnetofection, enhanced DNA uptake into human glioblastoma-astrocytoma, epithelial-like cell line U-87 MG, hepatocellular carcinoma Hep G2, cervical cancer HeLa and breast cancer MDA-MB-231 cells. Having confirmed this, we monitored uptake of plasmid DNA mediated by ternary magnetoplexes by fluorescence microscopy, flow cytometry and reporter gene expression assays in the presence and absence of a magnetic field. Our observations clearly indicate enhanced transfection efficiency in vitro, upon magnetofection, in the presence of serum as seen from β-Gal reporter gene expression. The observed activity in serum suggests the suitability of MNPs for in vivo applications. Further, we measured the transverse relaxation time (T2) and obtained T2-weighted MRI images of treated U-87 MG cells. T2 determined for MNP-VP-Me22 and MNP-VP-Et22 corresponds to 22.6±0.8 ms and 36.0±2.1 ms, respectively, as compared to 47±1.7 ms for control, suggesting their applicability in molecular imaging. Our results collectively highlight the potential of lipid-based approach to augment magnetic-field guided-gene delivery using MNPs and additionally towards developing intracellular molecular probes for magnetic resonance imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • DNA / administration & dosage*
  • DNA / chemistry
  • Ethanolamines / chemistry*
  • Humans
  • Liposomes
  • Magnetic Phenomena
  • Mice
  • Nanoparticles / chemistry*
  • Quaternary Ammonium Compounds / chemistry*
  • Transfection / methods*

Substances

  • Ethanolamines
  • Liposomes
  • N,N-di-n-hexadecyl-N,N-dihydroxyethylammonium
  • Quaternary Ammonium Compounds
  • DNA