Targeted delivery of small noncoding RNA for glioblastoma

Cancer Lett. 2021 Mar 1:500:274-280. doi: 10.1016/j.canlet.2020.11.004. Epub 2020 Nov 8.

Abstract

Aberrant expression of certain genes and microRNAs (miRNAs) has been shown to drive cancer development and progression, thus the modification of aberrant gene and miRNA expression presents an opportunity for therapeutic targeting. Ectopic modulation of a single dysregulated miRNA has the potential to revert therapeutically unfavorable gene expression in cancer cells by targeting multiple genes simultaneously. Although the use of noncoding RNA-based cancer therapy is a promising approach, the lack of a feasible delivery platform for small noncoding RNAs has hindered the development of this therapeutic modality. Recently, however, there has been an evolution in RNA nanotechnology, in which small noncoding RNA is loaded onto nanoparticles derived from the pRNA-3WJ viral RNA motif of the bacteriophage phi29. Preclinical studies have shown the capacity of this technology to specifically target tumor cells by conjugating these nanoparticles with ligands specific for cancer cells and resulting in the endocytic delivery of siRNA and miRNA inhibitors directly into the cell. Here we provide a systematic review of the various strategies, which have been utilized for miRNA delivery with a specific focus on the preclinical evaluation of promising RNA nanoparticles for glioblastoma (GBM) targeted therapy.

Keywords: Glioblastoma; RNA nanoparticle; RNA nanotechnology; microRNA; siRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / therapeutic use*
  • Nanoparticles / chemistry
  • Nanotechnology
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / therapeutic use*
  • RNA, Small Untranslated / chemistry
  • RNA, Small Untranslated / genetics
  • RNA, Small Untranslated / therapeutic use*
  • RNAi Therapeutics
  • Xenograft Model Antitumor Assays

Substances

  • MicroRNAs
  • RNA, Small Interfering
  • RNA, Small Untranslated