Document Detail


Targeted delivery of human VEGF gene via complexes of magnetic nanoparticle-adenoviral vectors enhanced cardiac regeneration.
MedLine Citation:
PMID:  22844395     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study assessed the concept of whether delivery of magnetic nanobeads (MNBs)/adenoviral vectors (Ad)-encoded hVEGF gene (Ad(hVEGF)) could regenerate ischaemically damaged hearts in a rat acute myocardial infarction model under the control of an external magnetic field. Adenoviral vectors were conjugated to MNBs with the Sulfo-NHS-LC-Biotin linker. In vitro transduction efficacy of MNBs/Ad-encoded luciferase gene (Ad(luc)) was compared with Ad(luc) alone in human umbilical vein endothelial cells (HUVECs) under magnetic field stimulation. In vivo, in a rat acute myocardial infarction (AMI) model, MNBs/Ad(hVEGF) complexes were injected intravenously and an epicardial magnet was employed to attract the circulating MNBs/Ad(hVEGF) complexes. In vitro, compared with Ad(luc) alone, MNBs/Ad(luc) complexes had a 50-fold higher transduction efficiency under the magnetic field. In vivo, epicardial magnet effectively attracted MNBs/Ad(hVEGF) complexes and resulted in strong therapeutic gene expression in the ischemic zone of the infarcted heart. When compared to other MI-treated groups, the MI-M(+)/Ad(hVEGF) group significantly improved left ventricular function (p<0.05) assessed by pressure-volume loops after 4 weeks. Also the MI-M(+)/Ad(hVEGF) group exhibited higher capillary and arteriole density and lower collagen deposition than other MI-treated groups (p<0.05). Magnetic targeting enhances transduction efficiency and improves heart function. This novel method to improve gene therapy outcomes in AMI treatment offers the potential into clinical applications.
Authors:
Yue Zhang; Wenzhong Li; Lailiang Ou; Weiwei Wang; Evgenya Delyagina; Cornelia Lux; Heiko Sorg; Kristina Riehemann; Gustav Steinhoff; Nan Ma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-26
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-07-30     Completed Date:  2012-11-28     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e39490     Citation Subset:  IM    
Affiliation:
Reference- and Translation Center for Cardiac Stem Cell Therapy, Department of Cardiac Surgery, University of Rostock, Rostock, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics*
Animals
Arterioles / metabolism
Capillaries / metabolism
Feasibility Studies
Heart / physiopathology*
Human Umbilical Vein Endothelial Cells / drug effects
Humans
Magnetic Fields
Magnets*
Male
Myocardial Infarction / genetics,  physiopathology,  therapy
Nanoparticles* / adverse effects
Rats
Regeneration*
Transfection / methods*
Vascular Endothelial Growth Factor A / genetics*
Chemical
Reg. No./Substance:
0/Vascular Endothelial Growth Factor A
Comments/Corrections

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