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Small interfering ribonucleic acid delivery with phase-shift nanoemulsions

Burgess, Mark T; Porter, Tyrone.
Proceedings of Meetings on Acoustics, 2013 - 19 (1): 75059

Acoustic cavitation offers a unique approach to small interfering RNA (siRNA) delivery compared to current methods. Typically, preformed microbubbles are used as cavitation nuclei to permeabilize cells and facilitate siRNA entry into the cytoplasm. However, microbubbles are restricted to the vasculature space and suffer from stability issues that limit their applicability. Alternatively, phase-shift nanoemulsions (PSNE) possess the long circulation and extravasation properties of nanoparticles, while also serving as cavitation nuclei in tissue upon acoustic droplet vaporization. Here we report the use of PSNE for delivery of siRNA engineered to knockdown green fluorescent protein (GFP) expression. A cell suspension (5x106 cells/mL) of GFP expressing breast adenocarcinoma cells was exposed to 5 MHz pulsed ultrasound (4 MPa peak negative pressure, 3 cycles, 250 Hz, 100 second exposure duration) in the presence of PSNE (~109/mL) and free siRNA (1.8 ┬ÁM). Flow cytometry was used to quantify GFP expression and cell viability. There was 20% (p

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