Enhanced Transfection Efficiency into Macrophages and Dendritic Cells by a Combination Method Using Mannosylated Lipoplexes and Bubble Liposomes with Ultrasound Exposure
Enhanced Transfection Efficiency into Macrophages and Dendritic Cells by a Combination Method Using Mannosylated Lipoplexes and Bubble Liposomes with Ultrasound Exposure
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DOI：
10.1089/hum.2009.106
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发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
--
作者：
Un, Keita;Kawakami, Shigeru;Hashida, Mitsuru
为了实现有效的基因治疗，需要选择性、高效地将治疗基因转染到靶细胞中。在这项研究中，我们开发了一种使用甘露糖化脂质复合物的组合方法，该方法对巨噬细胞和树突状细胞等抗原呈递细胞和气泡脂质体（BL）具有选择性，已知后者可以提高暴露于超声（US）时的转染效率。在以甘露糖受体表达而闻名的培养的小鼠巨噬细胞中，使用甘露糖化脂质复合物和 BL 与 US 的组合方法的转染效率高于裸露 pDNA 或未修饰的脂质复合物和 BL。在肝脏和脾脏中，这种组合方法的体内转染效率显着高于裸露的pDNA或未修饰的lipoplexes和BLs与US的转染效率。使用这种组合方法对肝非实质细胞的转染比肝实质细胞中的转染高约12倍。就脾转染活性而言，该组合方法对CD11c(+)细胞的转染效率明显高于CD11c(-)细胞。总之，我们证明，通过这种使用甘露糖化脂质复合物和 BL 与 US 暴露的组合方法，巨噬细胞和树突状细胞中的基因转染效率显着提高。
To achieve effective gene therapy, it is necessary to selectively and efficiently transfect therapeutic gene into targeted cells. In this study, we developed a combination method using mannosylated lipoplexes, which show selectivity to antigen-presenting cells such as macrophages and dendritic cells, and bubble liposomes (BLs), which are known to enhance transfection efficiency on exposure to ultrasound (US). In cultured mouse macrophages, known for the expression of mannose receptors, the transfection efficiency of this combination method using mannosylated lipoplexes and BLs with US was higher than that of naked pDNA or unmodified lipoplexes and BLs. In the liver and spleen, the in vivo transfection efficiency of this combination method was significantly higher than that of naked pDNA or unmodified lipoplexes and BLs with US. Transfection in hepatic non-parenchymal cells using this combination method was about 12 times higher than that in hepatic parenchymal cells. As far as splenic transfection activities were concerned, the transfection efficiency of this combination method in CD11c(+) cells was significantly higher than that in CD11c(-) cells. In conclusion, we demonstrated that the gene transfection efficiency in macrophages and dendritic cells was significantly increased by this combination method using mannosylated lipoplexes and BLs with US exposure.