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聚(甲基丙烯酸2-羟乙酯)-b-聚(L-赖氨酸)阳离子杂化材料用于在NIH 3T3小鼠胚胎成纤维细胞中的非病毒基因递送

Poly(2-hydroxyethyl methacrylate)-b-poly(L-Lysine) cationic hybrid materials for non-viral gene delivery in NIH 3T3 mouse embryonic fibroblasts.

作者信息

Johnson Renjith P, Uthaman Saji, John Johnson V, Heo Min Seon, Park In Kyu, Suh Hongsuk, Kim Il

机构信息

Department of Polymer Science and Engineering, BK21 PLUS Centre for Advanced Chemical Technology, Pusan National University, Republic of Korea.

出版信息

Macromol Biosci. 2014 Sep;14(9):1239-48. doi: 10.1002/mabi.201400071. Epub 2014 May 23.

Abstract

In order to develop efficient and nontoxic gene delivery vectors, a series of biocompatible block copolymers, poly[(2-hydroxyethyl methacrylate)40 -block-(L-lysine)n ] (n = 40, 80, 120, 150), are prepared by combining an atom transfer radical polymerization of 2-hydroxyethyl methacrylate with a ring-opening polymerization of N(ϵ) -(carbobenzoxy)-L-lysine N-carboxyanhydride. The block copolymers are successfully condensed with plasmid DNA (pDNA) into nanosized (<200 nm) polyplexes. As a representative sample, p(HEMA)40 -b-p(lys)150 is utilized to confirm the effective cellular and nuclear uptake of pDNA. The polymer/pDNA polyplexes exhibit very low cytotoxicity and enhanced transfection activity by being easily taken up into mouse embryonic fibroblast cell line (NIH 3T3). Thus, the chimeric block copolymers provide a means for developing versatile nonviral gene vectors harboring the ideal requirements of low cytotoxicity, good stability, and high transfection efficiency for gene therapy.

摘要

为了开发高效且无毒的基因递送载体,通过将甲基丙烯酸2-羟乙酯的原子转移自由基聚合与N(ε)-(苄氧羰基)-L-赖氨酸N-羧基酐的开环聚合相结合,制备了一系列生物相容性嵌段共聚物,聚[(甲基丙烯酸2-羟乙酯)40 -嵌段-(L-赖氨酸)n ](n = 40、80、120、150)。这些嵌段共聚物成功地与质粒DNA(pDNA)缩合形成纳米尺寸(<200 nm)的多聚体。作为代表性样品,聚(甲基丙烯酸2-羟乙酯)40 -b-聚(赖氨酸)150用于确认pDNA有效的细胞摄取和核摄取。聚合物/pDNA多聚体表现出非常低的细胞毒性,并通过易于被小鼠胚胎成纤维细胞系(NIH 3T3)摄取而增强了转染活性。因此,这种嵌合嵌段共聚物为开发具有低细胞毒性、良好稳定性和高转染效率等理想要求的通用非病毒基因载体提供了一种方法。

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