title: Intracellular Delivery of a Planar DNA Origami Structure by the Transferrin-Receptor Internalization Pathway.
abstract: DNA origami provides rapid access to easily functionalized, nanometer-sized structures making it an intriguing platform for the development of defined drug delivery and sensor systems. Low cellular uptake of DNA nanostructures is a major obstacle in the development of DNA-based delivery platforms. Herein, significant strong increase in cellular uptake in an established cancer cell line by modifying a planar DNA origami structure with the iron transport protein transferrin (Tf) is demonstrated. A variable number of Tf molecules are coupled to the origami structure using a DNA-directed, site-selective labeling technique to retain ligand functionality. A combination of confocal fluorescence microscopy and quantitative (qPCR) techniques shows up to 22-fold increased cytoplasmic uptake compared to unmodified structures and with an efficiency that correlates to the number of transferrin molecules on the origami surface.
authors.affiliation: Department of Molecular Biology and Genetics, University of Aarhus, C. F. Møllers Allé 3, 8000, Aarhus C, Denmark.|Center for DNA Nanotechnology and Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.
authors.forename: David H
authors.initials: DH
authors.lastname: Schaffert
authors.affiliation: Department of Molecular Biology and Genetics, University of Aarhus, C. F. Møllers Allé 3, 8000, Aarhus C, Denmark.|Center for DNA Nanotechnology and Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Okholm
authors.affiliation: Department of Molecular Biology and Genetics, University of Aarhus, C. F. Møllers Allé 3, 8000, Aarhus C, Denmark.|Center for DNA Nanotechnology and Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.
authors.forename: Rasmus S
authors.initials: RS
authors.lastname: Sørensen
authors.affiliation: Department of Molecular Biology and Genetics, University of Aarhus, C. F. Møllers Allé 3, 8000, Aarhus C, Denmark.|Center for DNA Nanotechnology and Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.
authors.forename: Jesper S
authors.initials: JS
authors.lastname: Nielsen
authors.affiliation: Center for DNA Nanotechnology and Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.|Department of Chemistry, University of Aarhus, Langelandsgade 140, 8000, Aarhus C, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tørring
authors.affiliation: Center for DNA Nanotechnology and Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.|Department of Chemistry, University of Aarhus, Langelandsgade 140, 8000, Aarhus C, Denmark.
authors.forename: Christian B
authors.initials: CB
authors.lastname: Rosen
authors.affiliation: Center for DNA Nanotechnology and Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.|Department of Chemistry, University of Aarhus, Langelandsgade 140, 8000, Aarhus C, Denmark.
authors.forename: Anne Louise B
authors.initials: AL
authors.lastname: Kodal
authors.affiliation: Center for DNA Nanotechnology and Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.|Department of Chemistry, University of Aarhus, Langelandsgade 140, 8000, Aarhus C, Denmark.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Mortensen
authors.affiliation: Center for DNA Nanotechnology and Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.|Department of Chemistry, University of Aarhus, Langelandsgade 140, 8000, Aarhus C, Denmark.
authors.forename: Kurt V
authors.initials: KV
authors.lastname: Gothelf
authors.affiliation: Department of Molecular Biology and Genetics, University of Aarhus, C. F. Møllers Allé 3, 8000, Aarhus C, Denmark.|Center for DNA Nanotechnology and Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Kjems
mesh_terms: D045744:Cell Line, Tumor; D003460:Crystallization / Q000379:methods; D004247:DNA / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000502:physiology; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000378:metabolism*; D010316:Particle Size; D011990:Receptors, Transferrin / Q000737:chemistry / Q000378:metabolism*; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism
chemical_list: D053769:Nanocapsules; D011990:Receptors, Transferrin; D004247:DNA
keywords: DNA origami; cell uptake; drug delivery; nanoparticles; transferrin