title: Combined targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles.
abstract: Targeting of viral vectors is a major challenge for in vivo gene delivery, especially after intravascular application. In addition, targeting of the endothelium itself would be of importance for gene-based therapies of vascular disease. Here, we used magnetic nanoparticles (MNPs) to combine cell transduction and positioning in the vascular system under clinically relevant, nonpermissive conditions, including hydrodynamic forces and hypothermia. The use of MNPs enhanced transduction efficiency of endothelial cells and enabled direct endothelial targeting of lentiviral vectors (LVs) by magnetic force, even in perfused vessels. In addition, application of external magnetic fields to mice significantly changed LV/MNP biodistribution in vivo. LV/MNP-transduced cells exhibited superparamagnetic behavior as measured by magnetorelaxometry, and they were efficiently retained by magnetic fields. The magnetic interactions were strong enough to position MNP-containing endothelial cells at the intima of vessels under physiological flow conditions. Importantly, magnetic positioning of MNP-labeled cells was also achieved in vivo in an injury model of the mouse carotid artery. Intravascular gene targeting can be combined with positioning of the transduced cells via nanomagnetic particles, thereby combining gene- and cell-based therapies.
authors.affiliation: Institute for Pharmacology and Toxicology, University of Bonn, D-53115 Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hofmann
authors.forename: Daniela
authors.initials: D
authors.lastname: Wenzel
authors.forename: Ulrich M
authors.initials: UM
authors.lastname: Becher
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Freitag
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Klein
authors.forename: Dietmar
authors.initials: D
authors.lastname: Eberbeck
authors.forename: Maike
authors.initials: M
authors.lastname: Schulte
authors.forename: Katrin
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Christian
authors.initials: C
authors.lastname: Bergemann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gleich
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Roell
authors.forename: Thomas
authors.initials: T
authors.lastname: Weyh
authors.forename: Lutz
authors.initials: L
authors.lastname: Trahms
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
authors.forename: Bernd K
authors.initials: BK
authors.lastname: Fleischmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeifer
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular; D005822:Genetic Vectors / Q000493:pharmacokinetics*; D016086:Lentivirus / Q000235:genetics; D008280:Magnetics; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D014161:Transduction, Genetic