Sonoporation of endothelial cells with CD31-targeted microbubbles at low acoustic pressures

Until now, targeted microbubbles have only been used for molecular imaging, not drug delivery. Drug uptake using microbubbles can be induced by sonoporation, a method that induces transient cell membrane pores by oscillating or jetting microbubbles so that therapeutics can enter the cell. So far, sonoporation has only been induced using non-targeted microbubbles. This study focuses on inducing sonoporation with CD31-targeted microbubbles in endothelial cells. Targeted microbubble-cell behavior upon insonification at 1 MHz (6× 10 cycle sine-wave bursts, 80 kPa peak negative acoustic pressure) was studied with a high-speed camera. The cell-impermeable propidium iodide (PI) was used as indicator for increased endothelial cell membrane permeability due to sonoporation. During insonification, the adhered microbubbles oscillated and were not destroyed. Cell deformation was not detected. Microbubbles larger than 3.0 µm or a relative vibration ≫ 0.5 induced PI uptake in the area surrounding the bubble. This study reveals that targeted microbubbles can induce sonoporation. This feature may now be used in molecular imaging using ultrasound, thereby combining imaging and drug delivery.