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用pH敏感的电荷转换聚(天冬酰胺)衍生物功能化的pDNA/聚(L-赖氨酸)多聚体用于向人脐静脉内皮细胞的可控基因递送

pDNA/poly(L-lysine) Polyplexes Functionalized with a pH-Sensitive Charge-Conversional Poly(aspartamide) Derivative for Controlled Gene Delivery to Human Umbilical Vein Endothelial Cells.

作者信息

Sanjoh Mai, Hiki Shigehiro, Lee Yan, Oba Makoto, Miyata Kanjiro, Ishii Takehiko, Kataoka Kazunori

机构信息

Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Japan.

出版信息

Macromol Rapid Commun. 2010 Jul 1;31(13):1181-6. doi: 10.1002/marc.201000056. Epub 2010 May 20.

DOI:10.1002/marc.201000056
PMID:21590873
Abstract

An efficient endosome-escaping function was integrated into the polyplex of plasmid DNA (pDNA) with poly(L-lysine) (PLys) to improve its gene transfection efficiency through electrostatic coating with charge-conversional polymer (CCP). CCP showed charge-conversional function responding to endosomal pH, leading to the release of pDNA/PLys polyplex into the cytoplasm. The cells took up the intact CCP-integrated ternary polyplex, which exerted appreciably higher transfection efficiency with lower cytotoxicity than pDNA/PLys polyplex against human umbilical vein endothelial cells (HUVECs). This is consistent with the facilitated endosomal escape of the CCP-integrated ternary polyplex compared to the pDNA/PLys polyplex as directly observed with confocal laser-scanning microscopy.

摘要

通过用电荷转换聚合物(CCP)进行静电包被,将一种高效的内体逃逸功能整合到质粒DNA(pDNA)与聚(L-赖氨酸)(PLys)的多聚体中,以提高其基因转染效率。CCP表现出对内体pH响应的电荷转换功能,导致pDNA/PLys多聚体释放到细胞质中。细胞摄取了完整的整合CCP的三元多聚体,与pDNA/PLys多聚体相比,其对人脐静脉内皮细胞(HUVECs)的转染效率明显更高,细胞毒性更低。这与共聚焦激光扫描显微镜直接观察到的整合CCP的三元多聚体比pDNA/PLys多聚体更容易从内体逃逸是一致的。

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