期刊
JOURNAL OF GENE MEDICINE
卷 10, 期 8, 页码 897-909出版社
WILEY
DOI: 10.1002/jgm.1208
关键词
colljugation; cardiovascular and pulmonary system; gene delivery; magnetic; poly ethyleneimine; nonviral vector
资金
- Sonderforschungsbereich/Transregio [37 B5, B2, A4]
- Helmholtz Gemeinschaft
- Mecklenburg-Vorpommern [0402710]
- BMBF BioChance PLUS [0313191]
- Miltenyi Biotec
- START-MSC project
- DAAD Project Based Personnel Exchange Programme with China
- Institute of implantation Technology and Biomaterials, Germany
- Steinbeis Transfer Zentrum fuer Herz-Kreislaufforschung, Rostock, Germany
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, PET) 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 (c) 2008 John Wiley & Sons, Ltd.
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