Aurora kinase B siRNA-loaded lactoferrin nanoparticles potentiate the efficacy of temozolomide in treating glioblastoma

Nanomedicine (Lond). 2018 Oct;13(20):2579-2596. doi: 10.2217/nnm-2018-0110. Epub 2018 Oct 18.

Abstract

Aim: To investigate the efficacy of lactoferrin nanoparticles (LfNPs) in delivering siRNA across the blood-brain barrier to treat glioblastoma multiforme (GBM) and with an additional objective of potentiation of conventional temozolomide (TMZ) chemotherapy.

Methods: Aurora kinase B (AKB) siRNA-loaded nanoparticles (AKB-LfNPs) were prepared with milk protein, lactoferrin, by water in oil emulsion method. AKB-LfNPs were tested in cell lines and in GBM orthotopic mouse model with and without TMZ treatment.

Results: AKB silencing, cytotoxicity and cell cycle arrest by these LfNPs were shown to be effective on GL261 cells. Tumor growth was significantly lower in AKB-LfNPs alone and in combination with TMZ treated mice and increased the survival by 2.5-times.

Conclusion: Treatment of AKB-LfNPs to GBM mice improves life expectancy and has potential to combine with conventional chemotherapy.

Keywords: blood–brain barrier; glioblastoma multiforme; nanoparticle; siRNA; temozolomide.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Aurora Kinase B / antagonists & inhibitors
  • Aurora Kinase B / genetics*
  • Blood-Brain Barrier / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dacarbazine / administration & dosage
  • Dacarbazine / chemistry
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Lactoferrin / administration & dosage*
  • Lactoferrin / chemistry
  • Mice
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / chemistry
  • Temozolomide / administration & dosage
  • Temozolomide / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • RNA, Small Interfering
  • Dacarbazine
  • AURKB protein, human
  • Aurora Kinase B
  • Lactoferrin
  • Temozolomide