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

Authors

Daxiang Cui, Shanghai Jiao Tong University, China
Chunlei Zhang, Shanghai Jiao Tong University, China
Bing Liu, Shanghai Jiao Tong University, China
Yi Shu, University of Kentucky
Tong Du, Shanghai Jiao Tong University, China
Dan Shu, University of Kentucky
Kan Wang, Shanghai Jiao Tong University, China
Fangping Dai, Ruhr-University of Bochum, Germany
Yanlei Liu, Shanghai Jiao Tong University, China
Chao Li, Shanghai Jiao Tong University, China
Fei Pan, Shanghai Jiao Tong University, China
Yuming Yang, Shanghai Jiao Tong University, China
Jian Ni, Shanghai Jiao Tong University, China
Hui Li, University of Kentucky
Beate Brand-Saberi, Ruhr-University of Bochum, Germany
Peixuan Guo, University of KentuckyFollow

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.

Document Type

Article

Publication Date

7-3-2015

Notes/Citation Information

Published in Scientific Reports, v. 5, article 10726, p. 1-14.

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Digital Object Identifier (DOI)

http://dx.doi.org/10.1038/srep10726

Funding Information

This work is supported by Chinese Key Basic Research Program (973 Project) (No. 2010CB933901 and 2015CB931802), the National Natural Scientific Foundation of China (Grant No. 81225010, 81327002, and 31170961) and NIH grants CA151648 (P.G.), EB019036 (P.G.) and EB012135 (P.G.). Funding to Peixuan Guo’s Endowed Chair in Nanobiotechnology at University of Kentucky is by the William Farish Endowment Fund. AFM images were obtained at Nanoimaging Core Facility supported by NIH SIG program and University of Nebraska Medical Center Program of ENRI to Luda Shlyakhtenko and Yuri Lyubchenko.

Repository Citation

Cui, Daxiang; Zhang, Chunlei; Liu, Bing; Shu, Yi; Du, Tong; Shu, Dan; Wang, Kan; Dai, Fangping; Liu, Yanlei; Li, Chao; Pan, Fei; Yang, Yuming; Ni, Jian; Li, Hui; Brand-Saberi, Beate; and Guo, Peixuan, "Regression of Gastric Cancer by Systemic Injection of RNA Nanoparticles Carrying Both Ligand and siRNA" (2015). Markey Cancer Center Faculty Publications. 36.
https://uknowledge.uky.edu/markey_facpub/36