Peptide generated anisotropic gold nanoparticles as efficient siRNA vectors

Int J Pharm. 2019 May 30:563:198-207. doi: 10.1016/j.ijpharm.2019.04.007. Epub 2019 Apr 3.

Abstract

Based on the cell penetrating ability of tryptophan-containing peptides, eight linear hexapeptides have been designed, synthesized and explored their efficiency toward the synthesis of gold nanoparticles under sunlight. The peptide generated gold nanoparticles (LP-GNPs) have been characterized by UV-visible spectroscopy, Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS) techniques. The binding ability of LP-GNPs toward siRNA, evaluated by gel electrophoresis indicates that sequence-selective-GNPs without any surface modifications exhibit strong affinity toward negatively charged biomolecules. Cellular uptake studies suggest that LP-GNPs exhibit significant uptake of fluorescence-labeled siRNA inside the cells as evidenced from Fluorescence Microscopy. In vitro gene silencing efficiency using newly generated GNPs revealed that above mentioned LP-GNPs efficiently down-regulate the level of GAPGH gene in colon cancer cells. Comparative gene silencing efficiency results indicate that anisotropic LP7-GNPs exhibit comparable efficacy to other existing carrier systems, such as Lipofectamine 2000 in presence of serum, mimicking in-vivo system. In conclusion, our results demonstrate that peptide-GNPs based delivery system for siRNA emerges to be effective to deliver RNAi therapeutics, uncovering new avenue in oncotherapy.

Keywords: GAPDH; Gene silencing; Gold nanoparticles; Peptide; siRNA.

MeSH terms

  • Arginine / administration & dosage*
  • Cell Survival / drug effects
  • Gene Transfer Techniques
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Gold / administration & dosage*
  • HCT116 Cells
  • Humans
  • Metal Nanoparticles / administration & dosage*
  • Oligopeptides / administration & dosage*
  • RNA, Small Interfering / administration & dosage*
  • Tryptophan / administration & dosage*

Substances

  • Oligopeptides
  • RNA, Small Interfering
  • Gold
  • Tryptophan
  • Arginine
  • Glyceraldehyde-3-Phosphate Dehydrogenases