Elucidating the Mechanisms Behind Sonoporation with Adeno-Associated Virus-Loaded Microbubbles
Elucidating the Mechanisms Behind Sonoporation with Adeno-Associated Virus-Loaded Microbubbles
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DOI：
10.1021/mp200112y
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发表时间：
2011-11-01
影响因子：
4.9
通讯作者：
De Smedt, Stefaan C.
中科院分区：
文献类型：
--
作者：
Geers, Bart;Lentacker, I.;De Smedt, Stefaan C.
微泡是美国食品药品监督管理局（FDA）批准的超声成像造影剂。据报道，由于所谓的声孔效应，在载药微泡上施加超声促进细胞对药物的摄取。然而，声致穿孔背后的生物物理学尚未完全理解。据信，声孔作用导致药物在细胞的细胞质中的“直接”递送，尽管也已经提出声孔作用促进内吞作用，这将改善药物被细胞内化。为了更好地理解声孔效应，本研究报道了超声辅助将腺相关病毒（AAV）负载在微泡表面的情况。AAV依赖于内吞作用来有效转导细胞，因此是评估内吞作用是否参与超声诱导的声孔作用的一种极好的工具。在载有AAV的微泡上应用超声显著改善了细胞对AAV的内化，尽管细胞的转导没有发生，表明通过声致孔作用，物质直接递送到细胞的胞质溶胶中。
Microbubbles are Food and Drug Administration (FDA) approved contrast agents for ultrasound imaging. It has been reported that applying ultrasound on drug-loaded microbubbles facilitates drug uptake by cells, due to so-named sonoporation. However, the biophysics behind sonoporation are not fully understood. It is believed that sonoporation results in a "direct" delivery of drugs in the cytoplasm of cells, though it has been suggested as well that sonoporation facilitates endocytosis which would improve the internalization of drugs by cells. To get a better understanding of sonoporation, this study reports on the ultrasound assisted delivery of adeno-associated virus (AAV) loaded on the surface of microbubbles. AAVs rely on endocytosis for efficient transduction of cells and are, consequently, an elegant tool to evaluate whether endocytosis is involved in ultrasound-induced sonoporation. Applying ultrasound on AAV-loaded microbubbles dearly improved the internalization of AAVs by cells, though transduction of the cells did not occur, indicating that by sonoporation substances become directly delivered in the cytosol of cells.