Grapefruit-derived Nanovectors Delivering Therapeutic miR17 Through an Intranasal Route Inhibit Brain Tumor Progression

Mol Ther. 2016 Feb;24(1):96-105. doi: 10.1038/mt.2015.188. Epub 2015 Oct 7.

Abstract

The lack of access to the brain is a major obstacle for central nervous system drug development. In this study, we demonstrate the capability of a grapefruit-derived nanovector (GNV) to carry miR17 for therapeutic treatment of mouse brain tumor. We show that GNVs coated with folic acid (FA-GNVs) are enhanced for targeting the GNVs to a folate receptor-positive GL-26 brain tumor. Additionally, FA-GNV-coated polyethylenimine (FA-pGNVs) not only enhance the capacity to carry RNA, but the toxicity of the polyethylenimine is eliminated by the GNVs. Intranasal administration of miR17 carried by FA-pGNVs led to rapid delivery of miR17 to the brain that was selectively taken up by GL-26 tumor cells. Mice treated intranasally with FA-pGNV/miR17 had delayed brain tumor growth. Our results demonstrate that this strategy may provide a noninvasive therapeutic approach for treating brain-related disease through intranasal delivery.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intranasal
  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Citrus paradisi / chemistry*
  • Disease Progression
  • Folic Acid / therapeutic use
  • Genetic Therapy / methods*
  • Mice
  • MicroRNAs / administration & dosage*
  • MicroRNAs / genetics*
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Organ Specificity
  • Plant Extracts / administration & dosage
  • Plant Extracts / chemistry
  • Polyethyleneimine / chemistry
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • MicroRNAs
  • Mirn17 microRNA, mouse
  • Plant Extracts
  • Polyethyleneimine
  • Folic Acid