摘要
聚乙烯亚胺(PEI)是一种阳离子聚合物,被广泛作为非病毒基因载体使用;然而,由于其细胞毒性限制它的广泛应用。PEI既可以是分枝构型也可以是线性构型。然而,分枝型聚乙烯亚胺(bPEI)具有更好地化学活性且在含盐条件下能够与DNA聚合形成更小的复合物,线性聚乙烯亚胺(lPEI)通常毒性更低且具有更高的转染效率。本文,我们将低分子量的lPEI与甲基-β-环糊精交联生成甲基-β-环糊精-线性聚乙烯亚胺(MLP)。并成功地通过NMR、FT-IR、MALDI-TOF和元素分析鉴定了MLP的结构。在标准血清转染环境下,MLP能够有效地使转染胶质母细胞瘤、黑色素瘤和肝癌细胞。其在血清中维持了一个高的转染率。除了其高的转染率,还发现MLP在不同的浓度范围内都表现出及其微小的细胞毒性,同时表现了低的离体细胞膜破坏能力。在未来的研究中MLP将成为一个有前景的基因投递系统。
关键词: 癌症,环糊精,基因投递,基因疗法,非病毒基因载体,聚乙烯亚胺
Current Gene Therapy
Title:Linear Poly(ethylenimine) Cross-Linked by Methyl-β-Cyclodextrin for Gene Delivery
Volume: 14 Issue: 4
Author(s): Wing-Fu Lai, David W. Green and Han-Sung Jung
Affiliation:
关键词: 癌症,环糊精,基因投递,基因疗法,非病毒基因载体,聚乙烯亚胺
摘要: Poly(ethylenimine) (PEI) is a cationic polymer extensively exploited for non-viral gene delivery; however, its wide application has been impeded by its cytotoxicity. PEI can assume either a branched or linear configuration. Whereas branched PEI (bPEI) is more chemically reactive and can form smaller complexes with DNA under salt-containing conditions, lPEI is generally less toxic and exhibits higher transfection efficiency. In this study, we cross-linked low-molecularweight lPEI with methyl β-cyclodextrin (MβCD) to form MβCD-lPEI (MLP). The structure of MLP was successfully characterized by NMR, FT-IR, MALDI-TOF and elemental analysis. In the standard serum-free transfection environment, MLP could effectively transfect glioblastoma, melanoma and hepatocarcinoma cells. A high transfection efficiency was maintained in the presence of serum. Apart from its high transfection efficiency, MLP was found to have negligible cytotoxicity over a wide range of concentrations and to exhibit a low membrane disruptive capacity ex vivo. MLP warrants further development as a promising gene delivery system for future research.
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Cite this article as:
Lai Wing-Fu, Green W. David and Jung Han-Sung, Linear Poly(ethylenimine) Cross-Linked by Methyl-β-Cyclodextrin for Gene Delivery, Current Gene Therapy 2014; 14 (4) . https://dx.doi.org/10.2174/1566523214666140612160042
DOI https://dx.doi.org/10.2174/1566523214666140612160042 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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