Aptamer-Conjugated Gold Nanoparticles Targeting Epidermal Growth Factor Receptor Variant III for the Treatment of Glioblastoma

Int J Nanomedicine. 2020 Feb 28:15:1363-1372. doi: 10.2147/IJN.S238206. eCollection 2020.

Abstract

Purpose: In this study, we constructed novel brain-targeting complexes (U2-AuNP) by conjugating aptamer U2 to the gold nanoparticle (AuNPs) surface as a promising option for GBM therapy.

Materials and methods: The properties of the U2-AuNP complexes were thoroughly characterized. Then, we detected the in vitro effects of U2-AuNP in U87-EGFRvIII cell lines and the in vivo antitumor effects of U2-AuNP in GBM-bearing mice. Furthermore, we explored the inhibition mechanism of U2-AuNP in U87-EGFRvIII cell lines.

Results: We found that U2-AuNP inhibits the proliferation and invasion of U87-EGFRvIII cell lines and prolongs the survival time of GBM-bearing mice. We found that U2-AuNP can inhibit the EGFR-related pathway and prevent DNA damage repair in GBM cells.

Conclusion: These results reveal the promising potential of U2-AuNP as a drug candidate for targeted therapy in GBM.

Keywords: EGFRvIII; GBM; SELEX; therapy.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / pharmacology*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Proliferation
  • ErbB Receptors / antagonists & inhibitors*
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Gold / chemistry*
  • Humans
  • Male
  • Metal Nanoparticles / administration & dosage*
  • Metal Nanoparticles / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Aptamers, Nucleotide
  • epidermal growth factor receptor VIII
  • Gold
  • ErbB Receptors