Ultrasound-enhanced transgene expression in vascular cells is not dependent upon cavitation-induced free radicals

Allan Lawrie, Axel F Brisken, Sheila E Francis, David Wyllie, Endre Kiss-Toth, Eva E Qwarnstrom, Stephen K Dower, David C. Crossman, Christopher M Newman

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61 Citations (Scopus)

Abstract

Although acoustic cavitation is clearly important in ultrasound (US)-enhanced gene delivery (UEGD), the relative importance of mechanical and sonochemical (free radical) bioeffects remains unclear, as does the mechanism of gene delivery at the cellular level. Porcine vascular smooth muscle cells (VSMC) were transfected with luciferase or green fluorescent protein (GFP) plasmid +/- pulsed 956 kHz US (2.0 mechanical index (MI), 128 W cm(-2) spatial peak pulse average intensity, ISPPA) for 60 s, in the presence or absence of 20 mM cysteamine or N-acetyl-L-cysteine. Both compounds effectively scavenged free radical production following US, leaving unaffected the 50- to 100-fold enhancements in luciferase expression seen in US-treated VSMC. US exposure enhanced plasmid uptake (25 +/- 4.6 vs. 3 +/- 1.9 cells/field, n=4, psevenfold) and average fluorescence intensity (>sixfold) of GFP-transfected cells. UEGD is not dependent upon cavitation-induced free radical generation and has potential for use with a wide range of therapeutic transgenes.
Original languageEnglish
Pages (from-to)1453-1461
Number of pages9
JournalUltrasound in Medicine & Biology
Volume29
Issue number10
DOIs
Publication statusPublished - 2003

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