Regression of Gastric Cancer by Systemic Injection of RNA Nanoparticles Carrying both Ligand and siRNA

Sci Rep. 2015 Jul 3:5:10726. doi: 10.1038/srep10726.

Abstract

Gastric cancer is the second leading cause of cancer-related death worldwide. RNA nanotechnology has recently emerged as an important field due to recent finding of its high thermodynamic stability, favorable and distinctive in vivo attributes. Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models. In vitro assay revealed that the RNA nanoparticles specifically bind to gastric cancer cells, and knock-down the BRCAA1 gene. Apoptosis of gastric cancer cells was observed. Animal trials confirmed that these RNA nanoparticles could be used to image gastric cancer in vivo, while showing little accumulation in crucial organs and tissues. The volume of gastric tumors noticeably decreased during the course of treatment. No damage to important organs by RNA nanoparticles was detectible. All the results indicated that this novel RNA nanotechnology can overcome conventional cancer therapeutic limitations and opens new opportunities for specific delivery of therapeutics to stomach cancer without damaging normal cells and tissues, reduce the toxicity and side effect, improve the therapeutic effect, and exhibit great potential in clinical tumor therapy.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Apoptosis
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Knockdown Techniques
  • Genetic Therapy
  • Humans
  • Injections, Intravenous
  • Inverted Repeat Sequences
  • Mice, Nude
  • Nanoparticles / administration & dosage*
  • Nanoparticles / adverse effects
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Organ Specificity
  • RNA Interference
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / adverse effects
  • RNA, Small Interfering / genetics
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Tumor Burden

Substances

  • ARID4B protein, human
  • Antigens, Neoplasm
  • Neoplasm Proteins
  • RNA, Small Interfering