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Enhanced thoracic gene delivery by magnetic nanobead-mediated vector
The journal of gene medicine, 2008-08, Vol.10 (8), p.897-909
Li, Wenzhong
Ma, Nan
Ong, Lee-Lee
Kaminski, Alexander
Skrabal, Christian
Ugurlucan, Murat
Lorenz, Peter
Gatzen, Hans-Heinrich
Lützow, Karola
Lendlein, Andreas
Pützer, Brigitte M.
Li, Ren-Ke
Steinhoff, Gustav
2008
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Li, Wenzhong
Ma, Nan
Ong, Lee-Lee
Kaminski, Alexander
Skrabal, Christian
Ugurlucan, Murat
Lorenz, Peter
Gatzen, Hans-Heinrich
Lützow, Karola
Lendlein, Andreas
Pützer, Brigitte M.
Li, Ren-Ke
Steinhoff, Gustav
Titel
Enhanced thoracic gene delivery by magnetic nanobead-mediated vector
Ist Teil von
The journal of gene medicine, 2008-08, Vol.10 (8), p.897-909
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
Erscheinungsjahr
2008
Quelle
MEDLINE
Beschreibungen/Notizen
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. Copyright © 2008 John Wiley & Sons, Ltd.
Sprache
Englisch
Identifikatoren
ISSN: 1099-498X
eISSN: 1521-2254
DOI: 10.1002/jgm.1208
Titel-ID: cdi_proquest_miscellaneous_69357261
Format
–
Schlagworte
Animals
,
cardiovascular and pulmonary system
,
conjugation
,
DNA - genetics
,
DNA - metabolism
,
Feasibility Studies
,
gene delivery
,
Gene therapy
,
Gene Transfer Techniques
,
Genetic Therapy - methods
,
Genetic Vectors - drug effects
,
magnetic
,
Magnetics
,
Mice
,
Mice, Inbred C57BL
,
Nanoparticles - chemistry
,
nonviral vector
,
poly ethyleneimine
,
Polyethyleneimine - metabolism
,
Polyethyleneimine - pharmacology
,
Thorax - metabolism
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