Identification of magnetic nanoparticles for combined positioning and lentiviral transduction of endothelial cells.
OBJECTIVE
The combination of magnetic nanoparticles (MNPs) with a magnetic field is a powerful approach to enable cell positioning and/or local gene therapy. Because physical requirements for MNPs differ between these two applications we have explored whether the use of different MNPs can provide site-specific positioning combined with efficient viral transduction of endothelial cells (ECs).


METHODS
A variety of MNPs was screened for magnetic cell labeling and lentivirus binding. Then two different MNPs were chosen and their combined application was evaluated regarding EC magnetization and transduction efficiency.


RESULTS
The combined use of PEI-Mag2 and NDT-Mag1 particles provided both efficient lentiviral transduction and high magnetic responsiveness of ECs that could be even retained within the vascular wall under flow conditions. The use of these MNPs did not affect biological characteristics of ECs like surface marker expression and vascular network formation. Importantly, with this method we could achieve an efficient functional overexpression of endothelial nitric oxide synthase in ECs.


CONCLUSIONS
The application of two different MNPs provides optimal results for magnetic labeling of ECs in combination with viral transduction. This novel approach could be very useful for targeted gene therapy ex vivo and site-specific cell replacement in the vascular system.
Institute of Physiology I, University of Bonn, Sigmund-Freud-Str 25, 53127 Bonn, Germany. dwenzel@uni-bonn.de
Daniela
D
Wenzel
Sarah
S
Rieck
Sarah
S
Vosen
Olga
O
Mykhaylyk
Christina
C
Trueck
Dietmar
D
Eberbeck
Lutz
L
Trahms
Katrin
K
Zimmermann
Alexander
A
Pfeifer
Bernd K
BK
Fleischmann
D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D015316:Genetic Therapy; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics*; D008280:Magnetics; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D014161:Transduction, Genetic