RNA Interference Nanotherapeutics for Treatment of Glioblastoma Multiforme

Mol Pharm. 2020 Nov 2;17(11):4040-4066. doi: 10.1021/acs.molpharmaceut.0c00709. Epub 2020 Oct 2.

Abstract

Nucleic acid therapeutics for RNA interference (RNAi) are gaining attention in the treatment and management of several kinds of the so-called "undruggable" tumors via targeting specific molecular pathways or oncogenes. Synthetic ribonucleic acid (RNAs) oligonucleotides like siRNA, miRNA, shRNA, and lncRNA have shown potential as novel therapeutics. However, the delivery of such oligonucleotides is significantly hampered by their physiochemical (such as hydrophilicity, negative charge, and instability) and biopharmaceutical features (in vivo serum stability, fast renal clearance, interaction with extracellular proteins, and hindrance in cellular internalization) that markedly reduce their biological activity. Recently, several nanocarriers have evolved as suitable non-viral vectors for oligonucleotide delivery, which are known to either complex or conjugate with these oligonucleotides efficiently and also overcome the extracellular and intracellular barriers, thereby allowing access to the tumoral micro-environment for the better and desired outcome in glioblastoma multiforme (GBM). This Review focuses on the up-to-date advancements in the field of RNAi nanotherapeutics utilized for GBM treatment.

Keywords: glioblastoma multiforme; miRNA; molecular pathways; nanocarriers; nucleic acid therapeutics; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy*
  • Genetic Therapy / methods*
  • Glioblastoma / drug therapy*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Mice
  • MicroRNAs / administration & dosage*
  • MicroRNAs / chemistry
  • MicroRNAs / genetics
  • Nanoconjugates / chemistry*
  • Oligonucleotides / administration & dosage*
  • Oligonucleotides / chemistry
  • Oligonucleotides / genetics
  • RNA Interference*
  • RNA, Long Noncoding / administration & dosage*
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / genetics
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • MicroRNAs
  • Nanoconjugates
  • Oligonucleotides
  • RNA, Long Noncoding
  • RNA, Small Interfering