Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles.
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.
Uchida
Masaki
M
Department of Chemistry and Biochemistry, and Center for Bio-Inspired Nanomaterials (CBIN), Montana State University, Bozeman, MT 59717, USA.
Flenniken
Michelle L
ML
Allen
Mark
M
Willits
Deborah A
DA
Crowley
Bridgid E
BE
Brumfield
Susan
S
Willis
Ann F
AF
Jackiw
Larissa
L
Jutila
Mark
M
Young
Mark J
MJ
Douglas
Trevor
T
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
D005290:Ferric Compounds; D010455:Peptides; D005293:Ferritins; D019793:Fluorescein