Receptor-mediated delivery of therapeutic RNA by peptide functionalized curdlan nanoparticles

Int J Biol Macromol. 2019 Apr 1:126:633-640. doi: 10.1016/j.ijbiomac.2018.12.152. Epub 2018 Dec 18.

Abstract

Natural carbohydrate polymer-based nanoparticles have great biocompatibility that is required for the safe delivery of various drugs including nucleic acid therapeutics. Herein, we designed curdlan-based nanoparticles for cancer cell targeted delivery of short interfering RNA (siRNA). iRGD peptide conjugated 6-amino-6-deoxy curdlan specifically delivered siRNA to integrin expressing cancer cells. Incubation of cancer cells with free iRGD peptide competitively blocked cellular uptake of the iRGD functionalized curdlan nanoparticles. Chloroquine but not nystatin inhibited cellular uptake of iRGD functionalized curdlan nanoparticles, indicating that the iRGD peptide conjugated curdlan nanoparticles were internalized through the receptor (clathrin)-mediated endocytosis. Moreover, a disease related gene Plk1 was substantially knocked down by siRNA carried by 6AC-iRGD nanoparticles in HepG2 cells. Our data suggested that iRGD functionalized curdlan may provide a biocompatible carrier for siRNA delivery.

Keywords: Cancer cells; Curdlan; Receptor-mediated endocytosis; iRGD; siRNA.

MeSH terms

  • Endocytosis
  • Gene Transfer Techniques*
  • Hep G2 Cells
  • Humans
  • Nanoparticles / chemistry*
  • Oligopeptides / chemistry*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / therapeutic use*
  • Receptors, Cell Surface / metabolism*
  • beta-Glucans / chemistry*

Substances

  • Oligopeptides
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • beta-Glucans
  • curdlan
  • arginyl-glycyl-aspartic acid