PEG-based block catiomers possessing DNA anchoring and endosomal escaping functions to form polyplex micelles with improved stability and high transfection efficacy
PEG-based block catiomers possessing DNA anchoring and endosomal escaping functions to form polyplex micelles with improved stability and high transfection efficacy
复制标题
DOI：
10.1016/j.jconrel.2007.06.020
复制
发表时间：
2007-10-08
影响因子：
10.8
通讯作者：
Kataoka, Kazunori
中科院分区：
文献类型：
--
作者：
Miyata, Kanjiro;Fukushima, Shigeto;Kataoka, Kazunori
为了在不产生大量聚阳离子的情况下显示出高的转染率，在聚乙二醇-b-阳离子聚(N-取代天冬酰胺)的氨基酸序列中引入了赖氨酸(Lys)单元作为DNA锚定单元，并在N-(2-氨基乙基)-2-氨基乙基(PEGb-Asp(Det)的侧翼引入了PEGb-P[Lys/Asp(Det)]，其中Asp(Det)单元作为缓冲单元诱导内膜逃逸，细胞毒性最小。PEG-b-P[Lys/Asp(Det)]/DNA复合体系在化学计量比N/P处的粒径分布较窄，约为90 nm，在化学计量比N/P处没有二次聚集体，表明形成了聚乙二醇屏蔽的复合胶束。在阳离子序列中引入Lys单元促进了细胞的摄取和100倍高水平的基因表达，即使在较低的N/P 2下也能制备出聚乙二醇b-P[Lys/Asp(Det)]/DNA复合胶束，这可能是由于锚定的Lys单元的结合能力增强所致。(C)2007爱思唯尔B.V保留所有权利。
For the development of polyplex systems showing a high transfection efficacy without a large excess of polycations, a lysine (Lys) unit as a DNA anchoring moiety was introduced into the amino acid sequence in poly(ethylene glycol)-b-cationic poly(N-substituted asparagine) with a flanking N-(2-aminoethyl)-2-aminoethyl group (PEG-b-Asp(DET)) resulting in PEG-b-P[Lys/Asp(DET)], in which the Asp(DET) unit acts as a buffering moiety inducing endosomal escape with minimal cytotoxicity. PEG-b-P[Lys/Asp(DET)]/DNA polyplexes exhibited a narrow size distribution of similar to 90 nm without secondary aggregates at the stoichiometric N/P 1, suggesting the formation of PEG-shielded polyplex micelles. The introduction of Lys units into the catiomer sequence facilitated cellular uptake and a 100-fold higher level of gene expression with PEG-b-P [Lys/Asp(DET)]/DNA polyplex micelles prepared even at a lowered N/P 2, possibly due to the enhanced association power of the anchoring Lys units. (c) 2007 Elsevier B.V All rights reserved.