Site directed vascular gene delivery in vivo by ultrasonic destruction of magnetic nanoparticle coated microbubbles

• Published in: Nanomedicine Vol. 8; no. 8; pp. 1309 - 1318
• Main Authors: Mannell, Hanna, PhD, Pircher, Joachim, MD, Fochler, Franziska, MS, Stampnik, Yvonn, MSc, Räthel, Thomas, PhD, Gleich, Bernhard, PhD, Plank, Christian, PhD, Mykhaylyk, Olga, PhD, Dahmani, Chiheb, MSc, Wörnle, Markus, MD, Ribeiro, Andrea, MSc, Pohl, Ulrich, MD, Krötz, Florian, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2012
• Subjects: Drug Delivery Systems; Endothelial Cells; Gene delivery; Gene Transfer Techniques; Genetic Therapy; Humans; Internal Medicine; Magnetic nanoparticles; Magnetite Nanoparticles - administration & dosage; Magnetite Nanoparticles - chemistry; Microbubbles; Plasmids; Ultrasonics; Ultrasound; Microbubbles; Gene delivery; Ultrasound; Endothelial cells; Magnetic nanoparticles
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2012.03.007

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 Editor This 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.