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通过接枝树枝状聚酰胺-胺提高生物可还原聚酰胺-胺的基因传递效率。

Improving gene delivery efficiency of bioreducible poly(amidoamine)s via grafting with dendritic poly(amidoamine)s.

机构信息

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

出版信息

Macromol Biosci. 2010 Apr 8;10(4):404-14. doi: 10.1002/mabi.200900300.

DOI:10.1002/mabi.200900300
PMID:20020519
Abstract

Dendritic poly(amidoamine)s (PAMAM)s were introduced into the side chains of disulfide-containing poly(amidoamine)s via repetitive Michael addition and amidation. The bioreducible poly(amidoamine)s grafted with dendritic polyamidoamines showed high buffer capacity, low cytotoxicity and strong DNA binding ability at low N/P ratio. They were able to condense DNA into small sized polycation/DNA complexes, which degraded and released the incorporated DNA under reductive conditions. In comparison to the original disulfide-containing poly(amidoamine) with aminoethyl side chain, the grafting of the bioreducible poly(amidoamine) with dendrimer greatly improved the transfection efficiencies of 293T and HeLa cells with foreign DNA at various N/P ratios. The structure-gene delivery property relations of dendrimer-grafted polycations will provide valuable insight into the design of highly efficient and less toxic polycationic gene carriers.

摘要

树枝状聚酰胺-胺(PAMAM)通过反复的迈克尔加成和酰胺化反应被引入含二硫键的聚酰胺-胺的侧链中。接枝有树枝状聚酰胺胺的还原性聚酰胺-胺具有较高的缓冲能力、低细胞毒性和在低 N/P 比下与 DNA 强结合能力。它们能够将 DNA 凝聚成小尺寸的聚阳离子/DNA 复合物,在还原条件下这些复合物能够降解并释放出所包含的 DNA。与具有氨乙基侧链的原始含二硫键的聚酰胺-胺相比,接枝有生物还原性聚酰胺-胺的树枝状聚合物大大提高了 293T 和 HeLa 细胞在不同 N/P 比下对外源 DNA 的转染效率。树枝状聚合物接枝聚阳离子的结构-基因传递性质关系将为设计高效、低毒的聚阳离子基因载体提供有价值的见解。

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