title: Targeted delivery of human VEGF gene via complexes of magnetic nanoparticle-adenoviral vectors enhanced cardiac regeneration.
abstract: 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: Reference- and Translation Center for Cardiac Stem Cell Therapy, Department of Cardiac Surgery, University of Rostock, Rostock, Germany.
authors: Yue
authors: Y
authors: Zhang
authors: Wenzhong
authors: W
authors: Li
authors: Lailiang
authors: L
authors: Ou
authors: Weiwei
authors: W
authors: Wang
authors: Evgenya
authors: E
authors: Delyagina
authors: Cornelia
authors: C
authors: Lux
authors: Heiko
authors: H
authors: Sorg
authors: Kristina
authors: K
authors: Riehemann
authors: Gustav
authors: G
authors: Steinhoff
authors: Nan
authors: N
authors: Ma
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D005240:Feasibility Studies; D006321:Heart / Q000503:physiopathology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D060526:Magnetic Fields; D059346:Magnets; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D053758:Nanoparticles / Q000009:adverse effects; D051381:Rats; D012038:Regeneration; D014162:Transfection / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A