Magnetic-silk/polyethyleneimine core-shell nanoparticles for targeted gene delivery into human breast cancer cells

Int J Pharm. 2019 Jan 30:555:322-336. doi: 10.1016/j.ijpharm.2018.11.030. Epub 2018 Nov 15.

Abstract

The lack of efficient and cost-effective methods for gene delivery has significantly hindered the applications of gene therapy. In this paper, a simple one step and cost effective salting-out method has been explored to fabricate silk-PEI nanoparticles (SPPs) and magnetic-silk/PEI core-shell nanoparticles (MSPPs) for targeted delivery of c-myc antisense oligodeoxynucleotides (ODNs) into MDA-MB-231 breast cancer cells. The size and zeta potential of the particles were controlled by adjusting the amount of silk fibroin in particle synthesis. Lower surface charges and reduced cytotoxicity were achieved for MSPPs compared with PEI coated magnetic nanoparticles (MPPs). Both SPPs and MSPPs were capable of delivering the ODNs into MDA-MB-231 cells and significantly inhibited the cell growth. Through magnetofection, high ODN uptake efficiencies (over 70%) were achieved within 20 min using MSPPs as carriers, exhibiting a significantly enhanced uptake effect compared to the same carriers via non-magnetofection. Both SPPs and MSPPs exhibited a significantly higher inhibition effect against MDA-MB-231 breast cancer cells compared to human dermal fibroblast (HDF) cells. Targeted ODN delivery was achieved using MSPPs with the help of a magnet, making them promising candidates for targeted gene therapy applications.

Keywords: Cancer; Gene delivery; Magnetic nanoparticles; Magnetofection; ODN; PEI; Silk.

Publication types

  • Comparative Study

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / therapy*
  • Cell Line
  • Cell Line, Tumor
  • Female
  • Fibroins / chemistry
  • Gene Targeting
  • Gene Transfer Techniques
  • Genes, myc / genetics
  • Genetic Therapy / methods
  • Humans
  • Magnetite Nanoparticles*
  • Nanoparticles*
  • Oligonucleotides, Antisense / administration & dosage*
  • Particle Size
  • Polyethyleneimine / chemistry
  • Silk / chemistry

Substances

  • Magnetite Nanoparticles
  • Oligonucleotides, Antisense
  • Silk
  • Polyethyleneimine
  • Fibroins