Sonoporation of endothelial cells in vivo

Ultrasound contrast agents as drug delivery systems are an emerging field. Recently, it was shown that targeted microbubbles (tMB) are able to sonoporate endothelial cells in vitro. This study investigates if tMB can also induce sonoporation in vivo, thereby making it possible to combine molecular imaging and drug delivery. Live chicken embryos were chosen as in vivo model. a_vβ₃-tMB attached to the vessel wall of the chicken embryo were insonified at 1MHz (1× 1000 cycles) at 200 kPa peak negative acoustic pressure. Sonoporation was studied optically using the model drug propidium iodide (PI). We observed 5% PI uptake when 1 or 2 tMB adhered, while this increased up to 80% when more than 10 tMB adhered. Ultrasound or tMB alone did not induce PI uptake. This in vivo study reveals that sonoporation can be induced using tMB at low acoustic pressure, without vessel rupture or extravasation of red blood cells. Further, it was shown that a higher MB concentration on the cell increased the efficiency of sonoporation.