title: Chlorotoxin bound magnetic nanovector tailored for cancer cell targeting, imaging, and siRNA delivery.
abstract: Ribonucleic acid interference (RNAi) is a powerful molecular tool that has potential to revolutionize the treatment of cancer. One major challenge of applying this technology for clinical application is the lack of site-specific carriers that can effectively deliver short interfering RNA (siRNA) to cancer cells. Here we report the development and assessment of a cancer-cell specific magnetic nanovector construct for efficient siRNA delivery and non-invasive monitoring through magnetic resonance imaging (MRI). The base of the nanovector construct is comprised of a superparamagnetic iron oxide nanoparticle core coated with polyethylene glycol (PEG)-grafted chitosan, and polyethylenimine (PEI). The construct was then further functionalized with siRNA and a tumor-targeting peptide, chlorotoxin (CTX), to improve tumor specificity and potency. Flow cytometry, quantitative RT-PCR, and fluorescence microscopy analyses confirmed receptor-mediated cellular internalization of nanovectors and enhanced gene knockdown through targeted siRNA delivery. The ability of this nanovector construct to generate specific contrast enhancement of glioblastoma cells was demonstrated through MR imaging. These findings suggest that this CTX enabled nanoparticle carrier may be well suited for delivery of RNAi therapeutics to brain cancer cells.
authors.affiliation: Department of Materials Science & Engineering, University of Washington, 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: Chen
authors.initials: C
authors.lastname: Fang
authors.forename: Ni
authors.initials: N
authors.lastname: Mu
authors.forename: Soumen
authors.initials: S
authors.lastname: Jana
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Leung
authors.forename: Hyejung
authors.initials: H
authors.lastname: Mok
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ellenbogen
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; D003102:Colloids; D003952:Diagnostic Imaging / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D012604:Scorpion Venoms / Q000378:metabolism*
chemical_list: D003102:Colloids; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D012604:Scorpion Venoms; C091539:Chlorotoxin; D049452:Green Fluorescent Proteins