title: RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model.
abstract: Systemic siRNA administration to target and treat glioblastoma, one of the most deadly cancers, requires robust and efficient delivery platform without immunogenicity. Here we report newly emerged multivalent naked RNA nanoparticle (RNP) based on pRNA 3-way-junction (3WJ) from bacteriophage phi29 to target glioblastoma cells with folate (FA) ligand and deliver siRNA for gene silencing. Systemically injected FA-pRNA-3WJ RNPs successfully targeted and delivered siRNA into brain tumor cells in mice, and efficiently reduced luciferase reporter gene expression (4-fold lower than control). The FA-pRNA-3WJ RNP also can target human patient-derived glioblastoma stem cells, thought to be responsible for tumor initiation and deadly recurrence, without accumulation in adjacent normal brain cells, nor other major internal organs. This study provides possible application of pRNA-3WJ RNP for specific delivery of therapeutics such as siRNA, microRNA and/or chemotherapeutic drugs into glioblastoma cells without inflicting collateral damage to healthy tissues.
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Lee
authors.affiliation: Department of Pharmaceutical Sciences, Nanobiotechnology Center, Markey Cancer Center, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
authors.forename: Farzin
authors.initials: F
authors.lastname: Haque
authors.affiliation: Department of Pharmaceutical Sciences, Nanobiotechnology Center, Markey Cancer Center, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Shu
authors.affiliation: Department of Neurological Surgery, Dardinger Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Yoo
authors.affiliation: Department of Pharmaceutical Sciences, Nanobiotechnology Center, Markey Cancer Center, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, Nanobiotechnology Center, Markey Cancer Center, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Yokel
authors.affiliation: Division of Neuropathology, Department of Pathology, University of Kentucky, Lexington, KY, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Horbinski
authors.affiliation: Department of Neurological Surgery, Dardinger Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Medical Center, Columbus, OH, USA.|ProteomeTech Inc., Seoul, Korea.
authors.forename: Tae Hyong
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Neurological Surgery, Dardinger Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Sung-Hak
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Neurological Surgery, Dardinger Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Medical Center, Columbus, OH, USA.|Neurosciences Research Program, Aurora Health Care Inc., Milwaukee, WI, USA.
authors.forename: Chang-Hyuk
authors.initials: CH
authors.lastname: Kwon
authors.affiliation: Department of Neurological Surgery, Dardinger Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakano
authors.affiliation: Department of Neurological Surgery, Dardinger Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Balveen
authors.initials: B
authors.lastname: Kaur
authors.affiliation: Department of Pharmaceutical Sciences, Nanobiotechnology Center, Markey Cancer Center, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
authors.forename: Peixuan
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D000067492:RNAi Therapeutics / Q000379:methods*; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering
keywords: glioblastoma; nanoparticle; pRNA; siRNA; three-way junction