Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles
Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles
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DOI：
10.1016/s0301-5629(03)00976-1
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发表时间：
2003-12-01
影响因子：
2.9
通讯作者：
Lindner, JR
中科院分区：
文献类型：
--
作者：
Christiansen, JP;French, BA;Lindner, JR
本研究的目的是通过超声（US）破坏携带质粒的微泡来评估基因转染的相对功效和机制。荧光素酶报告质粒与阳离子脂质微泡电荷偶联。大鼠后肢骨骼肌暴露于间歇性高功率US在剂量调整动脉内（IA）或IV管理的质粒轴承微泡通过颈动脉或颈静脉，分别。在第4天，在US暴露的骨骼肌中，IA的荧光素酶活性比IV施用携带质粒的微泡高200倍，并且与IM注射质粒（阳性对照）实现的转染相似。仅用US和IA注射质粒未发生转染。在给予微泡和US暴露后，小鼠提睾肌的活体显微镜检查显示荧光质粒的血管周围沉积，IA的程度是IV注射的两倍。电子显微镜检查显示，IA注射微泡后，US暴露肌肉中的肌细胞微孔程度更大。我们的结论是，肌肉转染由US破坏的质粒携带阳离子微泡放大IA，而不是电视，注射微泡由于更大的血管外沉积的质粒和更大程度的肌细胞微孔。（电子邮件：jlindner@virginia.edu）（C）2003年世界医学超声生物学联合会。
The aim of this study was to assess the relative efficacy and mechanism of gene transfection by ultrasound (US) destruction of plasmid-bearing microbubbles. Luciferase reporter plasmid was charge-coupled to cationic lipid microbubbles. Rat hindlimb skeletal muscle was exposed to intermittent high-power US during dose-adjusted intra-arterial (IA) or IV administration of plasmid-bearing microbubbles via the carotid artery or jugular vein, respectively. At 4 days, luciferase activity in US-exposed skeletal muscle was 200-fold greater with IA than with IV administration of plasmid-bearing microbubbles, and was similar to transfection achieved by IM injection of plasmid (positive control). No transfection occurred with US and IA injection of plasmid alone. Intravital microscopy of the cremaster muscle in mice following administration of microbubbles and US exposure demonstrated perivascular deposition of fluorescent plasmid, the extent of which was twofold greater for IA compared to IV injection. Electron microscopy demonstrated a greater extent of myocellular microporations in US-exposed muscle after IA injection of microbubbles. We conclude that muscle transfection by US destruction of plasmid-bearing cationic microbubbles is amplified by IA, rather than TV, injection of microbubbles due to greater extravascular deposition of plasmid and to greater extent of myocellular microporation. (E-mail: jlindner@virginia.edu) (C) 2003 World Federation for Ultrasound in Medicine Biology.