Enhanced thoracic gene delivery by magnetic nanobead-mediated vector.
BACKGROUND
Systemic gene delivery is limited by the adverse hydrodynamic conditions on the collection of gene carrier particles to the specific area. In the present study, a magnetic field was employed to guide magnetic nanobead (MNB)/polymer/DNA complexes after systemic administration to the left side of the mouse thorax in order to induce localized gene expression.


METHODS
Nonviral polymer (poly ethyleneimine, PEI) vector-gene complexes were conjugated to MNBs with the Sulfo-NHS-LC-Biotin linker. In vitro transfection efficacy of MNB/PEI/DNA was compared with PEI/DNA in three different cell lines as well as primary endothelial cells under magnetic field stimulation. In vivo, MNB/PEI/DNA complexes were injected into the tail vein of mice and an epicardial magnet was employed to attract the circulating MNB/PEI/DNA complexes.


RESULTS
Endocytotic uptake of MNB/PEI/DNA complexes and intracellular gene release with nuclear translocation were observed in vitro, whereas the residues of MNB/PEI complexes were localized at the perinuclear region. Compared with PEI/DNA complexes alone, MNB/PEI/DNA complexes had a 36- to 85-fold higher transfection efficiency under the magnetic field. In vivo, the epicardial magnet effectively attracted MNB/PEI/DNA complexes in the left side of the thorax, resulting in strong reporter and therapeutic gene expression in the left lung and the heart. Gene expression in the heart was mainly within the endothelium.


CONCLUSIONS
MNB-mediated gene delivery could comprise a promising method for gene delivery to the lung and the heart.
Li
Wenzhong
W
Department of Cardiac Surgery, University of Rostock, Rostock, Germany.
Ma
Nan
N
Ong
Lee-Lee
LL
Kaminski
Alexander
A
Skrabal
Christian
C
Ugurlucan
Murat
M
Lorenz
Peter
P
Gatzen
Hans-Heinrich
HH
Lützow
Karola
K
Lendlein
Andreas
A
Pützer
Brigitte M
BM
Li
Ren-Ke
RK
Steinhoff
Gustav
G
D000818:Animals; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005240:Feasibility Studies; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000187:drug effects*; D008280:Magnetics; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D011094:Polyethyleneimine / Q000378:metabolism / Q000494:pharmacology*; D013909:Thorax / Q000378:metabolism
D011094:Polyethyleneimine; D004247:DNA