Effect of chitosan-alginate nanoparticles and ultrasound on the efficiency of gene transfection of human cancer cells

J Gene Med. 2010 Feb;12(2):168-79. doi: 10.1002/jgm.1418.

Abstract

Background: Gene therapy has been used to treat a variety of health problems, but transfection inefficiency and the lack of safe vectors have limited clinical progress. Fabrication of a vector that is safe and has high transfection efficiency is crucial for the development of successful gene therapy. The present study aimed to synthesize chitosan-alginate nanoparticles that can be used as carriers of the pAcGFP1-C1 plasmid and to use these nanoparticles with an ultrasound protocol to achieve high efficiency gene transfection.

Methods: Chitosan was complexed with alginate and the pAcGFP1-C1 plasmid at different charge ratios to create chitosan-alginate-DNA nanoparticles (CADNs). The average particle size and loading efficiency were measured. Plasmid DNA retardation and integrity were analysed on 1% agarose gels. The effect of CADNs and ultrasound on the efficiency of transfection of cells and subcutaneous tumors was evaluated.

Results: In the CADNs, the average size of incorporated plasmid DNA was 600-650 nm and the loading efficiency was greater than 90%. On the basis of the results of the plasmid DNA protection test, CADNs could protect the transgene from DNase I degradation. The transgene product expression could be enhanced efficiently if cells or tumor tissues were first given CADNs and then treated with ultrasound.

Conclusions: The use of CADNs combined with an ultrasound regimen is a promising method for safe and effective gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry*
  • Alginates / toxicity
  • Animals
  • Cell Death / drug effects
  • Chitosan / chemistry*
  • Chitosan / toxicity
  • DNA / genetics
  • Electrophoresis, Agar Gel
  • Glucuronic Acid / chemistry
  • Glucuronic Acid / toxicity
  • HeLa Cells
  • Hexuronic Acids / chemistry
  • Hexuronic Acids / toxicity
  • Humans
  • Mice
  • Microscopy, Fluorescence
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Neoplasms / metabolism*
  • Plasmids / genetics
  • Transfection / methods*
  • Ultrasonics*

Substances

  • Alginates
  • Hexuronic Acids
  • Glucuronic Acid
  • DNA
  • Chitosan