Doxorubicin and anti-VEGF siRNA co-delivery via nano-graphene oxide for enhanced cancer therapy in vitro and in vivo

Int J Nanomedicine. 2018 Jun 27:13:3713-3728. doi: 10.2147/IJN.S162939. eCollection 2018.

Abstract

Background: Graphene oxide (GO) has attracted intensive interest in biological and medical fields in recent years due to its unique physical, chemical, and biological properties. In our previous work, we proved that GO could deliver small interfering RNA (siRNA) into cells and downregulate the expression of the desired gene.

Methods: This study investigated the potential of a modified GO nanocarrier for co-delivery of siRNA and doxorubicin (DOX) for enhanced cancer therapy. Fourier transform infrared spectroscopy, laser particle size analyzer, UV-visible spectroscopy, gel electrophoresis retardation, and in vitro release assay were studied.

Results: The results of real-time polymerase chain reaction revealed that the expression of vascular endothelial growth factor (VEGF) mRNA was decreased 46.84%±3.72% (mean ± SD). Enzyme-linked immunosorbent assay indicated that the expression of VEGF protein was down-regulated to 52.86%±1.10% (mean ± SD) in vitro. In vivo tumor growth assay GO-poly-l-lysine hydrobromide/folic acid (GPF)/DOX/siRNA exhibited gene silencing and tumor inhibition (66.95%±2.35%, mean ± SD) compared with naked siRNA (1.62%±1.47%, mean ± SD) and DOX (33.63%±5.85%, mean ± SD). GPF/DOX/siRNA exhibited no testable cytotoxicity.

Conclusion: The results indicated that co-delivery of siRNA and DOX by GPF could be a promising application in tumor clinical therapy.

Keywords: cervical carcinoma; co-delivery carrier; graphene oxide; siRNA delivery.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use*
  • Drug Delivery Systems*
  • Drug Liberation
  • Folic Acid / chemistry
  • Gene Silencing / drug effects
  • Graphite / chemistry*
  • HeLa Cells
  • Humans
  • Mice, Inbred ICR
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Polylysine / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • Ribonuclease, Pancreatic / antagonists & inhibitors
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • Static Electricity
  • Tumor Burden / drug effects
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • RNA, Messenger
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A
  • Polylysine
  • Graphite
  • Doxorubicin
  • Folic Acid
  • Ribonuclease, Pancreatic