Methotrexate-Coated Complexes of Plasmid DNA and Polyethylenimine for Gene Delivery
Methotrexate-Coated Complexes of Plasmid DNA and Polyethylenimine for Gene Delivery
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DOI：
10.1248/bpb.b18-00144
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发表时间：
2018-10-01
影响因子：
2
通讯作者：
Sasaki, Hitoshi
中科院分区：
文献类型：
--
作者：
Kodama, Yukinobu;Noda, Ryo;Sasaki, Hitoshi
叶酸受体在癌细胞表面过表达。采用静电结合法成功构建了甲氨蝶呤（MTX）-质粒DNA-聚乙烯亚胺（pDNA-PEI）复合物（PEI复合物）基因递送载体。稳定的阴离子纳米颗粒在MTX电荷比为120或更高时进行优化。pDNA PEI MTX复合物（MTX复合物）在小鼠黑素瘤细胞系B16-F10中显示出与阳离子pDNA PEI复合物一样高的基因表达效率。MTX复合物通过叶酸受体被细胞特异性摄取机制摄取。MTX包被的复合物可用作内吞作用配体。MTX 120复合物没有表现出血液聚集。MTX 120复合物静脉给药后在肝脏和脾脏中的转基因效率高于PEI复合物。因此，MTX复合物有望成为一种新型的基因载体。
Folate receptors are overexpressed on the surface cancer cells. We successfully constructed a new gene delivery vector of methotrexate (MTX)-coated plasmid DNA polyethylenimine (pDNA-PEI) complexes (PEI complexes) by electrostatic binding. The stable anionic nanoparticle was optimized at MTX charge ratios of 120 or more. pDNA PEI MTX complexes (MTX complexes) demonstrated gene expression efficiency as high as cationic pDNA PEI complexes in the mouse melanoma cell line, B16-F10. The MTX complexes were taken up by the cell-specific uptake mechanisms via the folate receptor. MTX-coated complexes are useful as endocytosis ligands. The MTX120 complexes exhibited no blood aggregation. The transgene efficiency of MTX120 complexes in the liver and spleen after their intravenous administration was higher than that of PEI complexes. Therefore, MTX complexes are expected as a new gene vector in the future.