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

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.

Graphical AbstractLocal vascular gene delivery in vivo by magnetic trapping of pDNA coated microbubbles. Magnetic microbubbles (MMB) coated with pDNA coding for dsRed were administered systemically (1) MMB were retained at the vessel wall in the dorsal skin fold chamber (left upper photo) by magnetic field application (2) and MMB were destroyed on ultrasound (3) 48-72 h after treatment dsRed expression was observed in the endothelium in the dorsal skin (4) but not in vessels of the cremaster muscle (right upper photo). The combination of magnetic targeting and ultrasound mediated MMB rupture resulted in high site specificity of gene delivery.Figure optionsDownload high-quality image (240 K)Download as PowerPoint slide