Gene delivery system based on highly specific recognition of surface-vimentin with N-acetylglucosamine immobilized polyethylenimine

Gene delivery system based on highly specific recognition of surface-vimentin with N-acetylglucosamine immobilized polyethylenimine
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DOI:
10.1016/j.biomaterials.2010.12.062
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发表时间:
2011-05-01
期刊:
影响因子:
14
通讯作者:
Akaike, Toshihiro
Akaike, Toshihiro
中科院分区:
工程技术1区
文献类型:
--
作者:
Kim, Sun-Jung;Ise, Hirohiko;Akaike, Toshihiro

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使用碳水化合物固定化的基因和药物递送系统可用于特异性靶向凝集素表达组织。在这里,我们报道 N-乙酰氨基葡萄糖 (GlcNAc) 与聚乙烯亚胺 (GlcNAc-PEI) 与表达波形蛋白的细胞(如 293FT 和 HeLa 细胞)特异性相互作用。最近,据报道中间丝波形蛋白和结蛋白在细胞表面具有 GlcNAc 结合凝集素样特性。因此,GlcNAc 缀合剂可以靶向表达波形蛋白和结蛋白的细胞和组织。使用GlcNAc-PEI将绿色荧光蛋白和荧光素酶基因高效转染表达Vimentin的293FT和HeLa细胞;这些基因在波形蛋白敲低细胞中的表达较低。共聚焦显微镜分析表明,GlcNAc-PEI 复合物与 HeLa 细胞表面的波形蛋白相互作用。这些结果表明 GlcNAc-PEI/DNA 复合物通过波形蛋白被 293FT 和 HeLa 细胞特异性摄取。我们建议这种基因传递系统可用于靶向表达波形蛋白的各种细胞,例如成纤维细胞和肿瘤细胞。 (C) 2011 Elsevier Ltd. 保留所有权利。
Gene and drug-delivery systems that use immobilization of carbohydrates are useful for the specific targeting of lectin-expressing tissues. Here, we report that N-acetylglucosamine (GlcNAc) with polyethylenimine (GlcNAc-PEI) specifically interacted with vimentin-expressing cells such as 293FT and HeLa cells. Recently, the intermediate filaments vimentin and desmin have been reported to have GlcNAc-binding lectin-like properties on the cell surface. Therefore, GlcNAc-conjugated agents can be targeted to vimentin- and desmin-expressing cells and tissues. Vimentin-expressing 293FT and HeLa cells were efficiently transfected with green fluorescent protein and luciferase genes by using GlcNAc-PEI; the expression of these genes in vimentin-knockdown cells were low. Confocal microscopic analysis showed that GlcNAc-PEI complexes interacted with vimentin on the cell surface of HeLa cells. These results demonstrate that GlcNAc-PEI/DNA complexes were specifically taken up by 293FT and HeLa cells via vimentin. We suggest that this gene-delivery system could be used to target various vimentin-expressing cells such as fibroblasts and tumor cells. (C) 2011 Elsevier Ltd. All rights reserved.