Development of anionic bubble lipopolyplexes for efficient and safe gene transfection with ultrasound exposure in mice
Development of anionic bubble lipopolyplexes for efficient and safe gene transfection with ultrasound exposure in mice
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DOI：
10.1016/j.jconrel.2013.12.023
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发表时间：
2014-02-28
影响因子：
10.8
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
--
作者：
Kurosaki, Tomoaki;Kawakami, Shigeru;Hashida, Mitsuru
阴离子气泡脂聚复合物已被开发为具有生物相容性化合物的阴离子超声（US）响应性基因递送载体，用于高效、安全地转染小鼠。阴离子泡脂聚复合物的颗粒约为450-600 nm，具有阴离子表面电荷。在没有US暴露的情况下，气泡脂复合物在人血管内皮细胞系EAhy 926中显示出极低的基因表达。然而，阴离子泡脂聚复合物将pDNA递送到细胞中而没有内吞作用，并且在US暴露后显示出显著高的基因表达。阴离子泡脂质复合物在EAhy 926细胞中表现出很小的细胞毒性，并且与红细胞几乎没有聚集。在小鼠静脉给药后，阴离子泡脂聚复合物仅在US暴露于腹部区域后在肝脏、肾脏和脾脏中显示高水平的基因表达。肝非实质细胞的基因表达水平明显高于实质细胞。此外，阴离子泡脂复合物没有显示出任何严重的肝毒性，也没有增强促炎细胞因子的产生。总体而言，我们已经成功地制备了阴离子泡脂质复合物，用于在小鼠中使用US暴露进行有效和安全的转染。(C)2013年爱思唯尔B。V.保留所有权利。
Anionic bubble lipopolyplexes have been developed as anionic ultrasound (US)-responsive gene delivery carriers with biocompatible compounds for efficient and safe transfection in mice. The particles of the anionic bubble lipopolyplexes were approximately 450-600 nm with an anionic surface charge. In the absence of US exposure, the bubble lipopolyplexes showed extremely low gene expression in the human vascular endothelial cell line EAhy926. The anionic bubble lipopolyplexes, however, delivered pDNA into cells without endocytosis and showed markedly high gene expression following US exposure. The anionic bubble lipopolyplexes showed little cytotoxicity in EAhy926 cells and little aggregation with erythrocytes. Following intravenous administration into mice, the anionic bubble lipopolyplexes showed high levels of gene expression in the liver, kidney, and spleen only after US exposure to the abdominal area. The level of gene expression in liver non-parenchymal cells was significantly higher than that in parenchymal cells. In addition, the anionic bubble lipopolyplexes did not show any severe hepatic toxicity and did not enhance the production of proinflammatory cytokines. Overall, we have succeeded in preparing anionic bubble lipopolyplexes for efficient and safe transfection with US exposure in mice. (C) 2013 Elsevier B. V. All rights reserved.