title: 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.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Nanobiotechnology Center, Markey Cancer Center, and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Du
authors.affiliation: Nanobiotechnology Center, Markey Cancer Center, and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Shu
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Kan
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Molecular Embryology, Ruhr-University of Bochum, 44780 Bochum, Germany.
authors.forename: Fangping
authors.initials: F
authors.lastname: Dai
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Pan
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ni
authors.affiliation: Nanobiotechnology Center, Markey Cancer Center, and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anatomy and Molecular Embryology, Ruhr-University of Bochum, 44780 Bochum, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Brand-Saberi
authors.affiliation: Nanobiotechnology Center, Markey Cancer Center, and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Peixuan
authors.initials: P
authors.lastname: Guo
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006801:Humans; D007275:Injections, Intravenous; D055029:Inverted Repeat Sequences; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D047368:Tumor Burden
chemical_list: C493892:ARID4B protein, human; D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering