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一种由聚酰胺-聚 N,N'-二(2-氨基乙基)氨基乙基谷氨酸共聚物组成的可生物降解和抗血清的基因传递载体。

A biodegradable and serum-resistant gene delivery carrier composed of polyamidoamine-poly N,N'-di-(2-aminoethyl) aminoethyl glutamine copolymer.

机构信息

The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2 Road, Guangzhou 510080, PR China.

出版信息

Colloids Surf B Biointerfaces. 2013 Apr 1;104:294-302. doi: 10.1016/j.colsurfb.2012.12.018. Epub 2012 Dec 31.

DOI:10.1016/j.colsurfb.2012.12.018
PMID:23337121
Abstract

Polyamidoamine-poly N,N'-di-(2-aminoethyl) aminoethyl glutamine graft copolymers (PAMAM-PAGA) were synthesized by polymerization of BLG-NCA and subsequent aminolysis with tris-(2-aminoethyl)-amine. The chemical structure and composition of the copolymers were characterized by FT-IR and (1)H NMR. The physicochemical and biological performances of the copolymers or copolymer/pDNA complexes were evaluated by enzyme-degradation, agarose gel retardation, stability test against DNase I, DLS measurement, MTT assay, CLSM observation and in vitro transfection. The copolymers were biodegradable and less cytotoxic; the copolymers could self-assemble with pDNA to form complexes which possessed stability against DNase I; the particle sizes were in 140-200 nm and the zeta potentials of the complexes were in +10±0.6 mV; the complexes displayed the enhanced transfection efficiency and excellent serum-resistant capacity. Therefore, the PAMAM-PAGA copolymer can be used as a biodegradable and serum-resistant gene delivery carrier.

摘要

聚酰胺-胺型树枝状大分子-聚 N,N'-二(2-氨乙基)乙二胺基丙基谷氨酸接枝共聚物(PAMAM-PAGA)通过 BLG-NCA 的聚合以及随后与三(2-氨乙基)胺的氨解反应合成。通过傅里叶变换红外光谱(FT-IR)和核磁共振氢谱(1H NMR)对共聚物的化学结构和组成进行了表征。通过酶降解、琼脂糖凝胶电泳阻滞、对 DNA 酶 I 的稳定性测试、动态光散射(DLS)测量、MTT 测定、CLSM 观察和体外转染评估了共聚物或共聚物/DNA 复合物的理化和生物学性能。共聚物可生物降解且细胞毒性较低;共聚物可以与 pDNA 自组装形成复合物,该复合物对 DNA 酶 I 具有稳定性;粒径在 140-200nm 之间,复合物的 zeta 电位在+10±0.6mV 之间;复合物显示出增强的转染效率和优异的耐血清能力。因此,PAMAM-PAGA 共聚物可用作可生物降解和耐血清的基因传递载体。

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