Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex

Nanomedicine. 2016 Oct;12(7):2201-2214. doi: 10.1016/j.nano.2016.05.016. Epub 2016 Jun 1.


Glioblastoma multiforme (GBM) is the most common and aggressive primary neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness, and drug resistance. microRNA-based therapeutics represent a promising approach due to their ability to inhibit multiple targets. In this work, we aim to restore the oncosuppressor activity of microRNA-34a (miR-34a) in GBM. We developed a cationic carrier system, dendritic polyglycerolamine (dPG-NH2), which remarkably improves miRNA stability, intracellular trafficking, and activity. dPG-NH2 carrying mature miR-34a targets C-MET, CDK6, Notch1 and BCL-2, consequently inhibiting cell cycle progression, proliferation and migration of GBM cells. Following complexation with dPG-NH2, miRNA is stable in plasma and able to cross the blood-brain barrier. We further show inhibition of tumor growth following treatment with dPG-NH2-miR-34a in a human glioblastoma mouse model. We hereby present a promising technology using dPG-NH2-miR-34a polyplex for brain-tumor treatment, with enhanced efficacy and no apparent signs of toxicity.

Keywords: Glioblastoma; MicroRNA-34a; Polyglycerol-based polyplex.

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Drug Carriers
  • Glioblastoma
  • Glycerol
  • Humans
  • MicroRNAs / pharmacology*
  • Polymers


  • Drug Carriers
  • MIRN34 microRNA, human
  • MicroRNAs
  • Polymers
  • polyglycerol
  • Glycerol