title: Non-viral VEGF(165) gene therapy--magnetofection of acoustically active magnetic lipospheres ('magnetobubbles') increases tissue survival in an oversized skin flap model.
abstract: 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.
authors.affiliation: Department of Plastic Surgery and Hand Surgery, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Holzbach
authors.forename: Dialekti
authors.initials: D
authors.lastname: Vlaskou
authors.forename: Iva
authors.initials: I
authors.lastname: Neshkova
authors.forename: Moritz A
authors.initials: MA
authors.lastname: Konerding
authors.forename: Klaus
authors.initials: K
authors.lastname: Wörtler
authors.forename: Olga
authors.initials: O
authors.lastname: Mykhaylyk
authors.forename: Bernd
authors.initials: B
authors.lastname: Gänsbacher
authors.forename: H-G
authors.initials: HG
authors.lastname: Machens
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.forename: Riccardo E
authors.initials: RE
authors.lastname: Giunta
mesh_terms: D000818:Animals; D062109:Dermatologic Surgical Procedures; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy / Q000379:methods*; D006085:Graft Survival / Q000502:physiology*; D008055:Lipids / Q000737:chemistry; D008280:Magnetics; D008297:Male; D008863:Microspheres; D055806:Microvessels / Q000502:physiology; D023421:Models, Animal; D009132:Muscles / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism; D016038:Skin Transplantation; D013524:Surgical Flaps / Q000098:blood supply; D014162:Transfection / Q000379:methods*; D014465:Ultrasonics; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D008055:Lipids; D042442:Vascular Endothelial Growth Factors