title: Site directed vascular gene delivery in vivo by ultrasonic destruction of magnetic nanoparticle coated microbubbles.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany. hanna.mannell@lrz.uni-muenchen.de
authors.forename: Hanna
authors.initials: H
authors.lastname: Mannell
authors.forename: Joachim
authors.initials: J
authors.lastname: Pircher
authors.forename: Franziska
authors.initials: F
authors.lastname: Fochler
authors.forename: Yvonn
authors.initials: Y
authors.lastname: Stampnik
authors.forename: Thomas
authors.initials: T
authors.lastname: Räthel
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gleich
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.forename: Olga
authors.initials: O
authors.lastname: Mykhaylyk
authors.forename: Chiheb
authors.initials: C
authors.lastname: Dahmani
authors.forename: Markus
authors.initials: M
authors.lastname: Wörnle
authors.forename: Andrea
authors.initials: A
authors.lastname: Ribeiro
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pohl
authors.forename: Florian
authors.initials: F
authors.lastname: Krötz
mesh_terms: D016503:Drug Delivery Systems; D042783:Endothelial Cells; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D045423:Microbubbles; D010957:Plasmids; D014465:Ultrasonics
chemical_list: D058185:Magnetite Nanoparticles