Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Japan.
Biomaterials. 2011 May;32(13):3471-80. doi: 10.1016/j.biomaterials.2010.12.062. Epub 2011 Feb 16.
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.
利用糖基化固定化的基因和药物传递系统可用于对凝集素表达组织的特异性靶向。在这里，我们报告称，N-乙酰葡萄糖胺（GlcNAc）与聚乙烯亚胺（GlcNAc-PEI）可特异性地与表达波形蛋白的细胞（如 293FT 和 HeLa 细胞）相互作用。最近，有报道称中间丝波形蛋白和结蛋白在细胞表面具有 GlcNAc 结合的凝集素样特性。因此，可将与 GlcNAc 缀合的试剂靶向到表达波形蛋白和结蛋白的细胞和组织。通过使用 GlcNAc-PEI，可有效转染表达绿色荧光蛋白和荧光素酶基因的 293FT 和 HeLa 细胞；在波形蛋白敲低细胞中，这些基因的表达水平较低。共焦显微镜分析显示，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 复合物可通过波形蛋白特异性地被 293FT 和 HeLa 细胞摄取。我们建议，这种基因传递系统可用于靶向各种表达波形蛋白的细胞，如成纤维细胞和肿瘤细胞。
