Efficient siRNA delivery system using carboxilated single-wall carbon nanotubes in cancer treatment

J Biomed Nanotechnol. 2012 Aug;8(4):567-74. doi: 10.1166/jbn.2012.1411.

Abstract

Several functionalized carbon nanotubes have been designed and tested for the purpose of nucleic acid delivery. In this study, the capacity of SWNTC-COOH for siRNA deliverey were investigated delivery in parallel with an efficient commercial system. Hep2G cells were reverse-transfected with 50 nM siRNA (p53 siRNA, TNF-alphasiRNA, VEGFsiRNA) using the siPORT NeoFX (Ambion) transfection agent in paralel with SWNTC-COOH, functionalised with siRNA. The highest level of gene inhibition was observed in the cases treated with p53 siRNA gene; in the case of transfection with siPort, the NeoFX value was 33.8%, while in the case of SWNTC-COOH as delivery system for p53 siRNA was 37.5%. The gene silencing capacity for VEGF was 53.7%, respectively for TNF-alpha 56.7% for siPORT NeoFX delivery systems versus 47.7% (VEGF) and 46.5% (TNF-alpha) for SWNTC-COOH delivery system. SWNTC-COOH we have been showed to have to be an efficient carrier system. The results from the inhibition of gene expresion for both transfection systems were confirmed at protein level. Overall, the lowest mRNA expression was confirmed at protein level, especially in the case of p53 siRNA and TNF-alpha siRNA transfection. Less efficient reduction protein expressions were observed in the case of VEGF siRNA, for both transfection systems at 24 h; only at 48 h, there was a statistically significant reduction of VEGF protein expression. SWCNT-COOH determined an efficient delivery of siRNA. SWNTC-COOH, combined with suitable tumor markers like p53 siRNA, TNFalpha siRNA or VEGF siRNA can be used for the efficient delivery of siRNA.

MeSH terms

  • Cell Survival / genetics
  • Drug Delivery Systems
  • Gene Silencing*
  • Hep G2 Cells
  • Humans
  • Nanotubes, Carbon / chemistry*
  • Nanotubes, Carbon / ultrastructure
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics*
  • Transfection / methods*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Vascular Endothelial Growth Factors / genetics
  • Vascular Endothelial Growth Factors / metabolism

Substances

  • Nanotubes, Carbon
  • RNA, Small Interfering
  • TP53 protein, human
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • Vascular Endothelial Growth Factors