title: In vivo risk evaluation of carbon-coated iron carbide nanoparticles based on short- and long-term exposure scenarios.
abstract: BACKGROUND
  While carbon-encapsulated iron carbide nanoparticles exhibit strong magnetic properties appealing for biomedical applications, potential side effects of such materials remain comparatively poorly understood. Here, we assess the effects of iron-based nanoparticles in an in vivo long-term study in mice with observation windows between 1 week and 1 year.
  
  
  METHODS
  Functionalized (PEG or IgG) carbon-encapsulated platinum-spiked iron carbide nanoparticles were injected intravenously in mice (single or repeated dose administration).
  
  
  RESULTS
  One week after administration, magnetic nanoparticles were predominantly localized in organs of the reticuloendothelial system, particularly the lung and liver. After 1 year, particles were still present in these organs, however, without any evident tissue alterations, such as inflammation, fibrosis, necrosis or carcinogenesis. Importantly, reticuloendothelial system organs presented with normal function.
  
  
  CONCLUSIONS
  This long-term exposure study shows high in vivo compatibility of intravenously applied carbon-encapsulated iron nanoparticles suggesting continuing investigations on such materials for biomedical applications.
authors.affiliation: Institute of Anesthesiology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.|Institute of Physiology & Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.|Department Materials Meet Life, Swiss Federal Laboratories for Materials Science & Technology (Empa), Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland.
authors.forename: Inge K
authors.initials: IK
authors.lastname: Herrmann
authors.affiliation: Institute of Anesthesiology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.|Institute of Physiology & Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Beck-Schimmer
authors.affiliation: ETH Zurich, Institute for Chemical & Bioengineering, Vladimir-Prelog-Weg 1-5/10, CH-8093 Zurich, Switzerland.
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Schumacher
authors.affiliation: ETH Zurich, Laboratory of Inorganic Chemistry, Vladimir-Prelog-Weg 1-5/10, CH-8093 Zurich, Switzerland.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gschwind
authors.affiliation: Center for Microscopy & Image Analysis, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Andres
authors.initials: A
authors.lastname: Kaech
authors.affiliation: Center for Microscopy & Image Analysis, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Ziegler
authors.affiliation: Swiss HPB & Transplant Center, Department of Surgery, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Clavien
authors.affiliation: ETH Zurich, Laboratory of Inorganic Chemistry, Vladimir-Prelog-Weg 1-5/10, CH-8093 Zurich, Switzerland.
authors.forename: Detlef
authors.initials: D
authors.lastname: Günther
authors.affiliation: ETH Zurich, Institute for Chemical & Bioengineering, Vladimir-Prelog-Weg 1-5/10, CH-8093 Zurich, Switzerland.
authors.forename: Wendelin J
authors.initials: WJ
authors.lastname: Stark
authors.affiliation: Swiss HPB & Transplant Center, Department of Surgery, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf
authors.affiliation: Swiss HPB & Transplant Center, Department of Surgery, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Schlegel
mesh_terms: D000818:Animals; D002244:Carbon / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D017554:Carbon Compounds, Inorganic / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D058085:Iron Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D059346:Magnets / Q000009:adverse effects / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects* / Q000032:analysis / Q000737:chemistry
chemical_list: D017554:Carbon Compounds, Inorganic; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D058085:Iron Compounds; C541825:iron carbide; D002244:Carbon
keywords: blood purification; long-term study; magnetic nanoparticles; targeted drug delivery