Targeted microbubble mediated sonoporation of endothelial cells in vivo
Targeted microbubble mediated sonoporation of endothelial cells in vivo
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DOI：
10.1109/tuffc.2014.006440
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发表时间：
2014-09
期刊：
影响因子：
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通讯作者：
I. Skachkov;Y. Luan;A. V. D. van der Steen;N. de Jong;K. Kooiman
中科院分区：
文献类型：
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作者：
I. Skachkov;Y. Luan;A. V. D. van der Steen;N. de Jong;K. Kooiman
超声造影剂作为药物输送系统是一个新兴的领域。最近，我们报道了靶向微泡能够在体外声致孔内皮细胞。在这项研究中，我们调查是否有针对性的微泡也可以在体内诱导内皮细胞的声穿孔，从而使联合收割机分子成像和药物输送。选择活鸡胚作为体内模型。以1 MHz、150 kPa（1 × 10000次循环）和200 kPa（1 × 1000次循环）峰值负声压声穿透附着在鸡胚血管壁上的α v β 3靶向微泡。使用模型药物碘化丙啶（PI）通过活体显微镜研究声穿孔。在150 kPa（n = 140）和200 kPa（n = 140）下，分别有48%和33%的微泡-血管-壁复合物中观察到内皮细胞PI摄取。PI摄取的效率取决于局部靶向微泡浓度，并且对于10至16个靶向微泡的簇增加高达80%。单独的超声或靶向微泡不诱导PI摄取。这种活体显微镜研究表明，声孔效应可以可视化，并在体内诱导使用靶向微泡。
Ultrasound contrast agents as drug-delivery systems are an emerging field. Recently, we reported that targeted microbubbles are able to sonoporate endothelial cells in vitro. In this study, we investigated whether targeted microbubbles can also induce sonoporation of endothelial cells in vivo, thereby making it possible to combine molecular imaging and drug delivery. Live chicken embryos were chosen as the in vivo model. αvß3-targeted microbubbles attached to the vessel wall of the chicken embryo were insonified at 1 MHz at 150 kPa (1 × 10 000 cycles) and at 200 kPa (1 × 1000 cycles) peak negative acoustic pressure. Sonoporation was studied by intravital microscopy using the model drug propidium iodide (PI). Endothelial cell PI uptake was observed in 48% of microbubble-vessel-wall complexes at 150 kPa (n = 140) and in 33% at 200 kPa (n = 140). Efficiency of PI uptake depended on the local targeted microbubble concentration and increased up to 80% for clusters of 10 to 16 targeted microbubbles. Ultrasound or targeted microbubbles alone did not induce PI uptake. This intravital microscopy study reveals that sonoporation can be visualized and induced in vivo using targeted microbubbles.