Nanoparticles Electrostatically Coated with Folic Acid for Effective Gene Therapy
Nanoparticles Electrostatically Coated with Folic Acid for Effective Gene Therapy
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DOI：
10.1021/mp2001268
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发表时间：
2011-05-01
影响因子：
4.9
通讯作者：
Kitahara, Takashi
中科院分区：
文献类型：
--
作者：
Kurosaki, Tomoaki;Morishita, Tamami;Kitahara, Takashi
我们开发了一种新型的载体，静电包覆的聚乙烯亚胺(PEI)/PDNA叶酸(FA)络合物。在没有共价结合的情况下，FA分子可以包覆在PEI/PDNA复合体上，在电荷比大于60时形成稳定的阴离子纳米颗粒。FA的加入显著降低了阳离子PEI/PDNA复合体对黑色素瘤细胞系B16-F10细胞的细胞毒作用，B16-F10细胞通常表达FA特异性受体(FR)。此外，阴离子FA60/PEI/PDNA复合体通过FR介导的途径在B16-F10细胞中显示出高的转基因效率。FA60/PEI/PDNA复合体与红细胞无凝集作用。小鼠静脉注射FA60/PEI/PDNA复合体后，在肝、肾、脾、肺等脏器中的转基因效率明显高于PEI/PDNA复合体。预先给予FA可显著抑制FA60/PEI/PDNA复合体的基因表达。因此，FA60/PEI/PDNA复合体可用于有效的基因治疗。
We developed a novel vector, electrostatically coated poly(ethylenimine) (PEI)/pDNA complexes with folic acid (FA). Without covalent binding, the FA molecules could coat the PEI/pDNA complexes, and stable anionic nanoparticles were formed at a charge ratio greater than 60. The addition of FA markedly decreased the cytotoxicity of the cationic PEI/pDNA complexes to the melanoma cell line, B16-F10 cells, which regularly expressed FA-specific receptor (FR). Furthermore, the anionic FA60/PEI/pDNA complexes showed high transgene efficiency via the FR-mediated pathway in B16-F10 cells. The FA60/PEI/pDNA complexes did not show agglutination with erythrocytes. After the intravenous injection of FA60/PEI/pDNA complexes into mice, a higher transgene efficiency than PEI/pDNA complexes was observed in the liver, kidney, spleen, and lung with FR. The gene expressions of FA60/PEI/pDNA complexes were significantly inhibited by preadministration of FA. Thus, the FA60/PEI/pDNA complexes were useful for effective gene therapy.