Anti-HER2 functionalized graphene oxide as survivin-siRNA delivery carrier inhibits breast carcinoma growth in vitro and in vivo

Drug Des Devel Ther. 2018 Sep 7:12:2841-2855. doi: 10.2147/DDDT.S169430. eCollection 2018.

Abstract

Background: The success of gene therapy is mostly dependent on the development of gene carrier. Graphene oxide (GO) possesses excellent aqueous solubility and biocompatibility, which is important for its biochemical and medical applications. Our previous work proved that GO can deliver siRNA into cells efficiently and downregulate the expression of desired protein.

Methods: In this study, a novel delivery carrier, GO-R8/anti-HER2 (GRH), was developed by conjugating octaarginine (R8) and anti-HER2 antibody with GO as a tumor active-targeting vector for survivin-siRNA delivery.

Results: GRH/survivin-siRNA formed nanoglobes of 195±10 nm in diameter. Real-time polymerase chain reaction analysis revealed that survivin messenger RNA expression showed a 42.4%±2.69% knockdown. The expression of survivin protein was downregulated to 50.86%±2.94% in enzyme-linked immunosorbent assay. In MTT tests, GRH exhibited no testable cytotoxicity. In vivo, GRH/survivin-siRNA showed gene silencing and inhibition of tumor growth.

Conclusion: The in vitro and in vivo results consistently demonstrated that GRH/survivin-siRNA has potential to be an efficient gene silencing carrier for siRNA delivery in cancer therapy.

Keywords: GO; anti-HER2 antibody; gene delivery; graphene oxide; nanocarrier; small interfering RNA; survivin-siRNA.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacology
  • Drug Delivery Systems*
  • Female
  • Graphite / chemistry
  • Graphite / pharmacology
  • Humans
  • MCF-7 Cells
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Oxides / chemistry
  • Oxides / pharmacology
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology*
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism
  • Structure-Activity Relationship
  • Survivin / chemistry
  • Survivin / genetics
  • Survivin / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Oligopeptides
  • Oxides
  • RNA, Small Interfering
  • Survivin
  • octaarginine
  • Graphite
  • Receptor, ErbB-2