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

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.

• Authors: Daxiang Cui, Chunlei Zhang, Bing Liu, Yi Shu, Tong Du, Dan Shu, Kan Wang, Fangping Dai, Yanlei Liu, Chao Li, Fei Pan, Yuming Yang, Jian Ni, Hui Li, Beate Brand-Saberi, Peixuan Guo
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 10726 (Jul 03 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26137913 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Animals
• Antigens, Neoplasm (genetics, 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, adverse effects)
• Neoplasm Proteins (genetics, metabolism)
• Organ Specificity
• RNA Interference
• RNA, Small Interfering (administration & dosage, adverse effects, genetics)
• Stomach Neoplasms (pathology, therapy)
• Tumor Burden