Chitosan-graft-polyethylenimine for Akt1 siRNA delivery to lung cancer cells

Int J Pharm. 2009 Aug 13;378(1-2):194-200. doi: 10.1016/j.ijpharm.2009.05.046. Epub 2009 Jun 6.

Abstract

Efficient delivery of small interfering RNA (siRNA) remains a challenging task in RNA interference (RNAi) studies. In this study, we used chitosan-graft-polyethylenimine (CHI-g-PEI) copolymer composed of chitosan and low molecular weight polyethylenimine (PEI) for the delivery of siRNA. The CHI-g-PEI carrier formed stable complexes with siRNA with compact spherical morphology. CHI-g-PEI delivered EGFP siRNA (siGFP) silenced EGFP expression nearly 2.5 folds higher than PEI25K at 50 pM siGFP concentration. Cell viability was found to be 2 folds high with CHI-g-PEI carrier than PEI25K. Also, our CHI-g-PEI carrier efficiently delivered Akt1 siRNA (siAkt) and thereby silenced onco-protein Akt1. Silencing of this crucial cell survival protein significantly reduced the lung cancer cell survival and proliferation. Additionally, Akt1 protein knock-down decreased A549 cell malignancy and metastasis. These findings suggest that the CHI-g-PEI carrier efficiently and safely delivered siRNA. Moreover, CHI-g-PEI mediated Akt1 siRNA delivery may emerge as a viable approach for lung cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • Chitosan / chemistry*
  • Gene Silencing
  • Genetic Vectors / chemistry
  • Green Fluorescent Proteins / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Polyethyleneimine / chemistry*
  • Polymers / chemistry
  • Proto-Oncogene Proteins c-akt / genetics*
  • RNA, Small Interfering / administration & dosage*

Substances

  • Polymers
  • RNA, Small Interfering
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Polyethyleneimine
  • Chitosan
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt