Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles

Jonathan P. Christiansen, Brent A. French, Alexander L. Klibanov, Sanjiv Kaul, Jonathan Lindner

Research output: Contribution to journalArticle

235 Scopus citations

Abstract

The aim of this study was to assess the relative efficacy and mechanism of gene transfection by ultrasound (US) destruction of plasmid-bearing microbubbles. Luciferase reporter plasmid was charge-coupled to cationic lipid microbubbles. Rat hindlimb skeletal muscle was exposed to intermittent high-power US during dose-adjusted intra-arterial (IA) or IV administration of plasmid-bearing microbubbles via the carotid artery or jugular vein, respectively. At 4 days, luciferase activity in US-exposed skeletal muscle was 200-fold greater with IA than with IV administration of plasmid-bearing microbubbles, and was similar to transfection achieved by IM injection of plasmid (positive control). No transfection occurred with US and IA injection of plasmid alone. Intravital microscopy of the cremaster muscle in mice following administration of microbubbles and US exposure demonstrated perivascular deposition of fluorescent plasmid, the extent of which was twofold greater for IA compared to IV injection. Electron microscopy demonstrated a greater extent of myocellular microporations in US-exposed muscle after IA injection of microbubbles. We conclude that muscle transfection by US destruction of plasmid-bearing cationic microbubbles is amplified by IA, rather than IV, injection of microbubbles due to greater extravascular deposition of plasmid and to greater extent of myocellular microporation.

Original languageEnglish (US)
Pages (from-to)1759-1767
Number of pages9
JournalUltrasound in Medicine and Biology
Volume29
Issue number12
DOIs
Publication statusPublished - Dec 2003
Externally publishedYes

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Keywords

  • Contrast agents
  • Contrast ultrasound
  • Gene delivery
  • Microbubbles
  • Plasmid
  • Ultrasound

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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