title: Optimization of magnetic nanoparticle-assisted lentiviral gene transfer.
abstract: OBJECTIVE
  Targeting of specific cells and tissues is of great interest for clinical relevant gene- and cell-based therapies. We use magnetic nanoparticles (MNPs) with a ferrimagnetic core (Fe(3)O(4)) with different coatings to optimize MNP-assisted lentiviral gene transfer with focus on different endothelial cell lines.
  
  
  METHODS
  Lentiviral vector (LV)/MNP binding was characterized for various MNPs by different methods (e.g. magnetic responsiveness measurement). Transduced cells were analyzed by flow cytometry, fluorescence microscopy and iron recovery. Cell transduction and cell positioning under physiological flow conditions were performed using different in vitro and ex vivo systems.
  
  
  RESULTS
  Analysis of diverse MNPs with different coatings resulted in identification of nanoparticles with improved LV association and enhanced transduction properties of complexes in several endothelial cell lines. The magnetic moments of LV/MNP complexes are high enough to achieve local gene targeting of perfused endothelial cells. Perfusion of a mouse aorta with LV/MNP transduced cells under clinically relevant flow conditions led to local cell attachment at the intima of the vessel.
  
  
  CONCLUSIONS
  MNP-guided lentiviral transduction of endothelial cells can be significantly enhanced and localized by using optimized MNPs.
authors.affiliation: Institute of Pharmacology and Toxicology, Biomedical Center, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Trueck
authors.forename: Katrin
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Olga
authors.initials: O
authors.lastname: Mykhaylyk
authors.forename: Martina
authors.initials: M
authors.lastname: Anton
authors.forename: Sarah
authors.initials: S
authors.lastname: Vosen
authors.forename: Daniela
authors.initials: D
authors.lastname: Wenzel
authors.forename: Bernd K
authors.initials: BK
authors.lastname: Fleischmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeifer
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008280:Magnetics; D051379:Mice; D053758:Nanoparticles; D019076:Transgenes