title: Uptake of ferromagnetic carbon-encapsulated metal nanoparticles in endothelial cells: influence of shear stress and endothelial activation.
abstract: OBJECTIVE
  Magnetic field guided drug targeting holds promise for more effective cancer treatment. Intravascular application of magnetic nanoparticles, however, bears the risk of potentially important, yet poorly understood side effects, such as off-target accumulation in endothelial cells.
  
  
  METHODS
  Here, we investigated the influence of shear stress (0-3.22 dyn/cm(2)), exposure time (5-30 min) and endothelial activation on the uptake of ferromagnetic carbon-encapsulated iron carbide nanomagnets into endothelial cells in an in vitro flow cell model.
  
  
  RESULTS
  We found that even moderate shear stresses typically encountered in the venous system strongly reduce particle uptake compared with static conditions. Interestingly, a pronounced particle uptake was observed in inflamed endothelial cells.
  
  
  CONCLUSIONS
  This study highlights the importance of relevant exposure scenarios accounting for physiological conditions when studying particle-cell interactions as, for example, shear stress and endothelial activation are major determinants of particle uptake. Such considerations are of particular importance with regard to successful translation of in vitro findings into (pre-)clinical end points.
authors.affiliation: Institute of Anesthesiology, University Hospital Zurich, Hof E 111, 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: Melanie
authors.initials: M
authors.lastname: Jacobson
authors.affiliation: Institute of Anesthesiology, University Hospital Zurich, Hof E 111, 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: Birgit
authors.initials: B
authors.lastname: Roth Z'graggen
authors.affiliation: Anthropological Institute & Museum, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Sereina M
authors.initials: SM
authors.lastname: Graber
authors.affiliation: ETH Zurich, Institute for Chemical & Bioengineering, Vladimir-Prelog-Weg 1, CH-8093 Zurich, Switzerland.
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Schumacher
authors.affiliation: ETH Zurich, Institute for Chemical & Bioengineering, Vladimir-Prelog-Weg 1, CH-8093 Zurich, Switzerland.
authors.forename: Wendelin J
authors.initials: WJ
authors.lastname: Stark
authors.affiliation: Center for Microscopy & Image Analysis, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Dumrese
authors.affiliation: Center for Microscopy & Image Analysis, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Mateos
authors.affiliation: Center for Microscopy & Image Analysis, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Aemisegger
authors.affiliation: Center for Microscopy & Image Analysis, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Ziegler
authors.affiliation: Institute of Anesthesiology, University Hospital Zurich, Hof E 111, 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: Martin
authors.initials: M
authors.lastname: Urner
authors.affiliation: Institute of Anesthesiology, University Hospital Zurich, Hof E 111, 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, Hof E 111, 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
mesh_terms: D002244:Carbon / Q000737:chemistry; D017554:Carbon Compounds, Inorganic / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D058085:Iron Compounds / Q000737:chemistry / Q000494:pharmacology; D060526:Magnetic Fields; D059346:Magnets / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D013314:Stress, Mechanical
chemical_list: D017554:Carbon Compounds, Inorganic; D058085:Iron Compounds; C541825:iron carbide; D002244:Carbon
keywords: cellular uptake; flow model; inflammation; magnetic nanoparticles