Ultrasound enhancement of cationic lipid-mediated gene transfer to primary tumors following systemic administration

K. Anwer, G. Kao, B. Proctor, I. Anscombe, V. Florack, R. Earls, E. Wilson, T. McCreery, E. Unger, A. Rolland, S. M. Sullivan

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

The impact of a localized application of ultrasound on gene transfer to primary tumors following systemic administration of cationic lipid based transfection complexes was investigated. We have previously shown that systemic administration of DOTMA (N-[(1-(2-3-dioleyloxy) propyl)]-N-N-N-trimethylammonium chloride): cholesterol-based transfection complexes to tumor-bearing mice resulted in expression in the tumor and other tissues, primarily the lungs. Application of ultrasound to the tumor before or after the injection resulted in a significant increase in gene transfer to the tumor with no increase observed in other tissues. The magnitude of increased expression ranged from three-to 270-fold depending upon the DNA dose. The following parameters were optimized for maximal increase: duration of ultrasound application, the time interval between plasmid injection and sonoporation, and plasmid dose. A combination of plasmid quantitation and fluorescence microscopy showed that ultrasound increased tumor uptake of the plasmid and that uptake was limited to the tumor vasculature. Using an IL-12 expression plasmid, the combination of a single plasmid dose (10 μg) and ultrasound treatment produced significantly higher levels of IL-12 in tumor. This increased expression was sufficient to inhibit tumor growth compared with the control conditions. These data demonstrate the potential application of sonoporation as an effective method for enhancing the expression of systemically administered genes in tumor endothelium for cancer gene therapy.

Original languageEnglish (US)
Pages (from-to)1833-1839
Number of pages7
JournalGene Therapy
Volume7
Issue number21
DOIs
StatePublished - 2000

Keywords

  • Cationic liposomes
  • IL-12
  • Plasmid
  • Systemic gene delivery
  • Tumor
  • Ultrasound

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Ultrasound enhancement of cationic lipid-mediated gene transfer to primary tumors following systemic administration'. Together they form a unique fingerprint.

Cite this