Sonoporation of endothelial cells by vibrating targeted microbubbles

Molecular imaging using ultrasound makes use of targeted microbubbles. In this study we investigated whether these microbubbles could also be used to induce sonoporation in endothelial cells. Lipid-coated microbubbles were targeted to CD31 and insonified at 1 MHz at low peak negative acoustic pressures at six sequences of 10 cycle sine-wave bursts. Vibration of the targeted microbubbles was recorded with the Brandaris-128 high-speed camera (~ 13 million frames per second). In total, 31 cells were studied that all had one microbubble (1.2–4.2 micron in diameter) attached per cell. After insonification at 80 kPa, 30% of the cells (n = 6) had taken up propidium iodide, while this was 20% (n = 1) at 120 kPa and 83% (n = 5) at 200 kPa. Irrespective of the peak negative acoustic pressure, uptake of propidium iodide was observed when the relative vibration amplitude of targeted microbubbles was greater than 0.5. No relationship was found between the position of the microbubble on the cell and induction of sonoporation. This study shows that targeted microbubbles can also be used to induce sonoporation, thus making it possible to combine molecular imaging and drug delivery.

Propidium iodide uptake by endothelial cell (in red) induced by microbubbles and diagnostic ultrasound. In fluorescence images: white lines = cell contours; green circles = position of microbubble. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)Figure optionsDownload as PowerPoint slide