title: Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles.
abstract: Protein cage architectures such as virus capsids and ferritins are versatile nanoscale platforms amenable to both genetic and chemical modification. Incorporation of multiple functionalities within these nanometer-sized protein architectures demonstrate their potential to serve as functional nanomaterials with applications in medical imaging and therapy. In the present study, we synthesized an iron oxide (magnetite) nanoparticle within the interior cavity of a genetically engineered human H-chain ferritin (HFn). A cell-specific targeting peptide, RGD-4C which binds alphavbeta3 integrins upregulated on tumor vasculature, was genetically incorporated on the exterior surface of HFn. Both magnetite-containing and fluorescently labeled RGD4C-Fn cages bound C32 melanoma cells in vitro. Together these results demonstrate the capability of a genetically modified protein cage architecture to serve as a multifunctional nanoscale container for simultaneous iron oxide loading and cell-specific targeting.
authors.affiliation: Department of Chemistry and Biochemistry, and Center for Bio-Inspired Nanomaterials (CBIN), Montana State University, Bozeman, MT 59717, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Uchida
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Flenniken
authors.forename: Mark
authors.initials: M
authors.lastname: Allen
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Willits
authors.forename: Bridgid E
authors.initials: BE
authors.lastname: Crowley
authors.forename: Susan
authors.initials: S
authors.lastname: Brumfield
authors.forename: Ann F
authors.initials: AF
authors.lastname: Willis
authors.forename: Larissa
authors.initials: L
authors.lastname: Jackiw
authors.forename: Mark
authors.initials: M
authors.lastname: Jutila
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Young
authors.forename: Trevor
authors.initials: T
authors.lastname: Douglas
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004354:Drug Screening Assays, Antitumor; D005290:Ferric Compounds / Q000737:chemistry* / Q000494:pharmacology; D005293:Ferritins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D019793:Fluorescein / Q000737:chemistry; D006801:Humans; D008280:Magnetics; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D005290:Ferric Compounds; D010455:Peptides; D005293:Ferritins; D019793:Fluorescein