title: Grapefruit-derived Nanovectors Delivering Therapeutic miR17 Through an Intranasal Route Inhibit Brain Tumor Progression.
abstract: The lack of access to the brain is a major obstacle for central nervous system drug development. In this study, we demonstrate the capability of a grapefruit-derived nanovector (GNV) to carry miR17 for therapeutic treatment of mouse brain tumor. We show that GNVs coated with folic acid (FA-GNVs) are enhanced for targeting the GNVs to a folate receptor-positive GL-26 brain tumor. Additionally, FA-GNV-coated polyethylenimine (FA-pGNVs) not only enhance the capacity to carry RNA, but the toxicity of the polyethylenimine is eliminated by the GNVs. Intranasal administration of miR17 carried by FA-pGNVs led to rapid delivery of miR17 to the brain that was selectively taken up by GL-26 tumor cells. Mice treated intranasally with FA-pGNV/miR17 had delayed brain tumor growth. Our results demonstrate that this strategy may provide a noninvasive therapeutic approach for treating brain-related disease through intranasal delivery.
authors.affiliation: Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Abhilash
authors.initials: A
authors.lastname: Samykutty
authors.affiliation: Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Mu
authors.affiliation: Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Pengxiao
authors.initials: P
authors.lastname: Cao
authors.affiliation: Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Rong
authors.affiliation: Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.affiliation: Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.|Robley Rex Veterans Administration Medical Center, Louisville, Kentucky, USA.
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D032083:Citrus paradisi / Q000737:chemistry*; D018450:Disease Progression; D005492:Folic Acid / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009928:Organ Specificity; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse; D010936:Plant Extracts; D011094:Polyethyleneimine; D005492:Folic Acid