title: Specific Delivery of MiRNA for High Efficient Inhibition of Prostate Cancer by RNA Nanotechnology.
abstract: Both siRNA and miRNA can serve as powerful gene-silencing reagents but their specific delivery to cancer cells in vivo without collateral damage to healthy cells remains challenging. We report here the application of RNA nanotechnology for specific and efficient delivery of anti-miRNA seed-targeting sequence to block the growth of prostate cancer in mouse models. Utilizing the thermodynamically ultra-stable three-way junction of the pRNA of phi29 DNA packaging motor, RNA nanoparticles were constructed by bottom-up self-assembly containing the anti-prostate-specific membrane antigen (PSMA) RNA aptamer as a targeting ligand and anti-miR17 or anti-miR21 as therapeutic modules. The 16 nm RNase-resistant and thermodynamically stable RNA nanoparticles remained intact after systemic injection in mice and strongly bound to tumors with little or no accumulation in healthy organs 8 hours postinjection, and subsequently repressed tumor growth at low doses with high efficiency.
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy; Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.|Nanobiotechnology Center, Markey Cancer Center and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Binzel
authors.affiliation: Nanobiotechnology Center, Markey Cancer Center and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy; Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.|Nanobiotechnology Center, Markey Cancer Center and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, USA.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, USA.
authors.forename: Qunshu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy; Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.|Nanobiotechnology Center, Markey Cancer Center and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Shu
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy; Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.|Nanobiotechnology Center, Markey Cancer Center and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Peixuan
authors.initials: P
authors.lastname: Guo
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D053758:Nanoparticles; D036103:Nanotechnology; D009690:Nucleic Acid Conformation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D034622:RNA Interference; D013816:Thermodynamics; D023041:Xenograft Model Antitumor Assays
chemical_list: D035683:MicroRNAs