具有侧链伯胺的聚（β-氨基酯）用于高效基因传递。

Poly(beta-aminoester)s with pendant primary amines for efficient gene delivery.

机构信息

Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.

出版信息

Bioconjug Chem. 2009 Dec;20(12):2317-23. doi: 10.1021/bc900317m.

DOI:10.1021/bc900317m

PMID:19938829

Abstract

Three hydrolytically degradable poly(beta-aminoester)s containing ester bonds in the main chain and primary amines in the side chain, synthesized by Michael polyaddition, were applied to deliver foreign DNA into cells in vitro. These linear polycations can condense DNA into small-sized particles with positive surface charge at high N/P ratios. Their high buffer capacity at pH 5-7 facilitated the escape of DNA from the endosome and resulted in efficient gene expression. Under the optimal conditions, poly(beta-aminoester)s with a pendant aminoethyl group showed higher transfection efficiencies than branched poly(ethylenimine) (PEI) 25KDa in 293T cells. The effect of side chain structure of the poly(beta-aminoester) on transfection efficiency has been investigated, which indicated that the poly(beta-aminoester) containing the pendant aminoethyl group was the most efficient carrier for both of 293T cells and COS-7 cells. The combination of hydrolytical degradation, high buffer capacity, relatively low cytotoxicity, and high transfection efficiency suggested that this kind of poly(beta-aminoester)s are novel promising nonviral gene carriers.

摘要

三种含有酯键的可水解聚（β-氨基酯）通过迈克尔加成反应合成，具有主链中的酯键和侧链中的伯胺，被应用于体外将外源 DNA 递送到细胞中。这些线性聚阳离子可以在高 N/P 比下将 DNA 凝聚成带正电荷的小颗粒。它们在 pH 5-7 时具有高缓冲能力，有助于 DNA 从内涵体中逃逸，从而实现高效的基因表达。在最佳条件下，带有侧链氨基乙基的聚（β-氨基酯）在 293T 细胞中的转染效率高于支化的聚乙烯亚胺（PEI）25 kDa。研究了聚（β-氨基酯）的侧链结构对转染效率的影响，结果表明，带有侧链氨基乙基的聚（β-氨基酯）对 293T 细胞和 COS-7 细胞都是最有效的载体。水解降解、高缓冲能力、相对低细胞毒性和高转染效率的结合表明，这种聚（β-氨基酯）是一种新型的有前途的非病毒基因载体。