Non-viral VEGF^sub 165^ gene therapy - magnetofection of acoustically active magnetic lipospheres ('magnetobubbles') increases tissue survival in an oversized skin flap model

Adenoviral transduction of the VEGF gene in an oversized skin flap increases flap survival and perfusion. In this study, we investigated the potential of magnetofection of magnetic lipospheres containing VEGF(165)-cDNA on survival and perfusion of ischemic skin flaps and evaluated the method with re...

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Published inJournal of cellular and molecular medicine Vol. 14; no. 3; p. 587
Main Authors Holzbach, Thomas, Vlaskou, Dialekti, Neshkova, Iva, Konerding, Moritz A, Wörtler, Klaus, Mykhaylyk, Olga, Gänsbacher, Bernd, Machens, H-G, Plank, Christian, Giunta, Riccardo E
Format Journal Article
LanguageEnglish
Published Bucharest Blackwell Publishing Ltd 01.03.2010
Subjects
Cells
Deoxyribonucleic acid
DNA
Gene therapy
Nanoparticles
Proteins
Signal transduction
Tissues
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Summary:Adenoviral transduction of the VEGF gene in an oversized skin flap increases flap survival and perfusion. In this study, we investigated the potential of magnetofection of magnetic lipospheres containing VEGF(165)-cDNA on survival and perfusion of ischemic skin flaps and evaluated the method with respect to the significance of applied magnetic field and ultrasound. We prepared perfluoropropane-filled magnetic lipospheres ('magnetobubbles') from Tween60-coated magnetic nanoparticles, Metafectene, soybean-oil and cDNA and studied the effect in an oversized random-pattern-flap model in the rats (n= 46). VEGF-cDNA-magnetobubbles were administered under a magnetic field with simultaneously applied ultrasound, under magnetic field alone and with applied ultrasound alone. Therapy was conducted 7 days pre-operative. Flap survival and necrosis were measured 7 days post-operatively. Flap perfusion, VEGF-protein concentration in target and surrounding tissue, formation and appearance of new vessels were analysed additionally. Magnetofection with VEGF-cDNA-magnetobubbles presented an increased flap survival of 50% and increased flap perfusion (P < 0.05). Without ultrasound and without magnetic field, the effect is weakened. VEGF concentration in target tissue was elevated (P < 0.05), while underlying muscle was not affected. Our results demonstrate the successful VEGF gene therapy by means of magnetobubble magnetofection. Here, the method of magnetofection of magnetic lipospheres is equally efficient as adenoviral transduction, but has a presumable superior safety profile. [PUBLICATION ABSTRACT]
ISSN:1582-1838