title: Cell transcytosing poly-arginine coated magnetic nanovector for safe and effective siRNA delivery.
abstract: Lack of safe and effective carriers for delivery of RNA therapeutics remains a barrier to its broad clinical application. We report the development of a cell tanscytosing magnetic nanovector engineered as an siRNA carrier. Iron oxide nanoparticles were modified with poly(ethylene glycol) (PEG), small interfering RNA (siRNA), and a cationic polymer layer. Three nanovector formulations with cationic polymer coatings of poly-arginine (pArg), polylysine (pLys), and polyethylenimine (PEI), respectively, were prepared. The three nanovector formulations where evaluated for safety and ability to promote gene silencing in three types of cancer cells C6/GFP(+), MCF7/GFP(+), and TC2/GFP(+), mimicking human cancers of the brain, breast, and prostate, respectively. Cell viability and fluorescence quantification assays revealed that pArg-coated nanovectors were most effective in promoting gene knockdown and least toxic of the three nanovector formulations tested. Transmission electron microscopy (TEM) imaging of nanovector treated cells further demonstrated that pArg-coated nanovectors enter cells through cell transcytosis, while pLys and PEI coated nanovectors enter cells endocytosis. Our findings suggest that NPs engineered to exploit the cell transcytosis intracellular trafficking pathway may offer a more safe and efficient route for siRNA delivery.
authors.affiliation: Department of Materials Science & Engineering, University of Washington, 302L Roberts Hall, Box 352120, Seattle, WA 98195, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Veiseh
authors.forename: Forrest M
authors.initials: FM
authors.lastname: Kievit
authors.forename: Hyejung
authors.initials: H
authors.lastname: Mok
authors.forename: Joseph
authors.initials: J
authors.lastname: Ayesh
authors.forename: Cassra
authors.initials: C
authors.lastname: Clark
authors.forename: Chen
authors.initials: C
authors.lastname: Fang
authors.forename: Matthew
authors.initials: M
authors.lastname: Leung
authors.forename: Hamed
authors.initials: H
authors.lastname: Arami
authors.forename: James O
authors.initials: JO
authors.lastname: Park
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005290:Ferric Compounds / Q000737:chemistry; D005822:Genetic Vectors / Q000009:adverse effects / Q000737:chemistry*; D006801:Humans; D008280:Magnetics; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D057900:Transcytosis / Q000502:physiology*; D014162:Transfection
chemical_list: D005290:Ferric Compounds; D010455:Peptides; D034741:RNA, Small Interfering; C000499:ferric oxide; C015462:polyarginine