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Site directed vascular gene delivery in vivo by ultrasonic destruction of magnetic nanoparticle coated microbubbles
Authors:Hanna Mannell  Joachim Pircher  Franziska Fochler  Yvonn Stampnik  Thomas Räthel  Bernhard Gleich  Christian Plank  Olga Mykhaylyk  Chiheb Dahmani  Markus Wörnle  Andrea Ribeiro  Ulrich Pohl  Florian Krötz
Institution:1. Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany;2. Medizinische Klinik and Poliklinik, Campus Innenstadt, Klinikum der Ludwig-Maximilians-University, München, Germany;3. Zentralinstitut für Medizintechnik (IMETUM), Technische Universität München, Garching, Germany;4. Institute of Experimental Oncology and Therapy Research, Technische Universität München, Munich, Germany;5. Institute of Energy Conversion Technology, Technische Universität München, Munich, Germany;6. Interventional Cardiology, Starnberg Community Hospital, Starnberg, Germany
Abstract:Site specific vascular gene delivery for therapeutic implications is favorable because of reduction of possible side effects. Yet this technology faces numerous hurdles that result in low transfection rates because of suboptimal delivery. Combining ultrasonic microbubble technology with magnetic nanoparticle enhanced gene transfer could make it possible to use the systemic vasculature as the route of application and to magnetically trap these compounds at the target of interest. In this study we show that magnetic nanoparticle-coated microbubbles bind plasmid DNA and successfully deliver it to endothelial cells in vitro and more importantly transport their cargo through the vascular system and specifically deliver it to the vascular wall in vivo at sites where microbubbles are retained by magnetic force and burst by local ultrasound application. This resulted in a significant enhancement in site specific gene delivery compared with the conventional microbubble technique. Thus, this technology may have promising therapeutic potential.From the Clinical EditorThis work focuses on combining ultrasonic microbubble technology with magnetic nanoparticle enhanced gene transfer to enable targeted gene delivery via the systemic vasculature and magnetic trapping of these compounds at the target of interest.
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