title: Accumulation of nano-sized particles in a murine model of angiogenesis.
abstract: OBJECTIVE
  To evaluate the ability of nm-scaled iron oxide particles conjugated with Azure A, a classic histological dye, to accumulate in areas of angiogenesis in a recently developed murine angiogenesis model.
  
  
  METHODS
  We characterised the Azure A particles with regard to their hydrodynamic size, zeta potential, and blood circulation half-life. The particles were then investigated by Magnetic Resonance Imaging (MRI) in a recently developed murine angiogenesis model along with reference particles (Ferumoxtran-10) and saline injections.
  
  
  RESULTS
  The Azure A particles had a mean hydrodynamic diameter of 51.8 ± 43.2 nm, a zeta potential of -17.2 ± 2.8 mV, and a blood circulation half-life of 127.8 ± 74.7 min. Comparison of MR images taken pre- and 24-h post-injection revealed a significant increase in R2(*) relaxation rates for both Azure A and Ferumoxtran-10 particles. No significant difference was found for the saline injections. The relative increase was calculated for the three groups, and showed a significant difference between the saline group and the Azure A group, and between the saline group and the Ferumoxtran-10 group. However, no significant difference was found between the two particle groups.
  
  
  CONCLUSIONS
  Ultrahigh-field MRI revealed localisation of both types of iron oxide particles to areas of neovasculature. However, the Azure A particles did not show any enhanced accumulation relative to Ferumoxtran-10, suggesting the accumulation in both cases to be passive.
authors: Department of Experimental Clinical Oncology, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark. Electronic address: Wittenborn@oncology.dk.
authors: Thomas R
authors: TR
authors: Wittenborn
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark; Department of Molecular Biology and Genetics, Aarhus University, C.F. Moellers Allé 3, 8000 Aarhus C, Denmark; The Lundbeck Foundation Nanomedicine Center for Individualized Management of Tissue Damage and Regeneration (LUNA), Aarhus University, Aarhus, Denmark.
authors: Esben K U
authors: EK
authors: Larsen
authors: Department of Experimental Clinical Oncology, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark.
authors: Thomas
authors: T
authors: Nielsen
authors: Center of Functionally Integrative Neuroscience (CFIN), Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark.
authors: Louise M
authors: LM
authors: Rydtoft
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark; Department of Molecular Biology and Genetics, Aarhus University, C.F. Moellers Allé 3, 8000 Aarhus C, Denmark; The Lundbeck Foundation Nanomedicine Center for Individualized Management of Tissue Damage and Regeneration (LUNA), Aarhus University, Aarhus, Denmark.
authors: Line
authors: L
authors: Hansen
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark; Department of Engineering, Aarhus University, Finlandsgade 22, 8000 Aarhus, Denmark.
authors: Jens V
authors: JV
authors: Nygaard
authors: The Lundbeck Foundation Nanomedicine Center for Individualized Management of Tissue Damage and Regeneration (LUNA), Aarhus University, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Bartholins Allé 6, 8000 Aarhus, Denmark.
authors: Thomas
authors: T
authors: Vorup-Jensen
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark; Department of Molecular Biology and Genetics, Aarhus University, C.F. Moellers Allé 3, 8000 Aarhus C, Denmark; The Lundbeck Foundation Nanomedicine Center for Individualized Management of Tissue Damage and Regeneration (LUNA), Aarhus University, Aarhus, Denmark.
authors: Jørgen
authors: J
authors: Kjems
authors: Department of Experimental Clinical Oncology, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark.
authors: Michael R
authors: MR
authors: Horsman
authors: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark; The Lundbeck Foundation Nanomedicine Center for Individualized Management of Tissue Damage and Regeneration (LUNA), Aarhus University, Aarhus, Denmark; Center for Insoluble Protein Structures (inSPIN) and Department of Chemistry, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark.
authors: Niels Chr
authors: NC
authors: Nielsen
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*; D010316:Particle Size; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles; D053769:Nanocapsules
keywords: Angiogenesis; Iron oxide particles; Sponge model; Ultrahigh-field MRI