Preparation of dendritic graft copolymer consisting of poly-(L-lysine) and arabinogalactan as a hepatocyte specific DNA carrier.
Preparation of dendritic graft copolymer consisting of poly-(L-lysine) and arabinogalactan as a hepatocyte specific DNA carrier.
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聚(L-赖氨酸)和阿拉伯半乳聚糖树状接枝共聚物的制备作为肝细胞特异性DNA载体。
DOI：
10.1080/10826069908544934
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发表时间：
1999
影响因子：
2.9
通讯作者：
A. Maruyama
中科院分区：
文献类型：
--
作者：
J. U. Park;T. Ishihara;A. Kano;T. Akaike;A. Maruyama
以聚L-赖氨酸（PLL）为主链，阿拉伯半乳聚糖（AG）为接枝物，制备了树枝状接枝共聚物（PAX）作为肝细胞特异性DNA载体。以NaBH_3CN为催化剂，通过AG的还原端与PLL的ε-氨基之间的还原胺化反应成功地制备了共聚物。从粗AG（Mn = 33 kDa）中分离低分子量级分（Mn = 25 kDa）对于反应进行是必不可少的。将所得共聚物通过超滤从未反应的AG中分离，并通过1H NMR和配备有多角度激光光散射检测器（GPC-MALLS）的凝胶渗透色谱法进行表征。DNA与肝癌细胞HepG 2的结合和内化通过将DNA与PAX共聚物络合而大大增强。在脱唾液酸糖蛋白受体（ASGP-R）竞争剂的存在下，PAX/DNA复合物与HepG 2细胞之间的相互作用被彻底抑制，表明该复合物对ASGP-R具有高度特异性。此外，PAX共聚物允许报告基因的表达。我们的研究结果表明，PAX共聚物可能提供一个新的研究工具，细胞特异性基因传递，并最终提高基因治疗技术。
The dendriTIc graft copolymers (PAX) consisting of a poly(L-lysine) (PLL) main chain and grafts of arabinogalactan (AG) were prepared as a liver cell-specific DNA carrier. The copolymers were successfully prepared by reductive amination reaction between a reductive end of AG and epsilon-amino groups of PLL using NaBH3CN as a catalyst. The fractionation of a low molecular weight fraction (Mn = 25 kDa) from a crude AG (Mn = 33 kDa) was essential for the reaction to proceed. The resulting copolymers were isolated by ultrafiltration from unreacted AG and characterized by 1H NMR and gel permeation chromatography equipped with a multiangle laser light scattering detector (GPC-MALLS). The binding and internalization of DNA to hepatoma cells, HepG2, were considerably enhanced by complexing DNA with PAX copolymers. The interactions between PAX/DNA complexes and HepG2 cells were thoroughly inhibited in the presence of a competitor to asialoglycoprotein receptors (ASGP-R), indicating high specificity of the complex to ASGP-R. Furthermore, the PAX copolymers allowed the expression of the reporter gene. Our results reveal that the PAX copolymers may provide a new research tool for cell-specific gene delivery and eventually enhance gene-therapy technology.
DOI：
10.1073/pnas.85.18.6949
发表时间：
1988-09-01
影响因子：
11.1
作者：
GABIZON, A;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D
体内受体介导的基因传递。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Wu,GY;Wilson,JM;Shalaby,F;Grossman,M;Shafritz,DA;Wu,CH
通讯作者：
Wu,CH