Zinc-Chelated Poly(1-vinylimidazole) and a Carbohydrate Ligand Polycation Form DNA Ternary Complexes for Gene Delivery
Zinc-Chelated Poly(1-vinylimidazole) and a Carbohydrate Ligand Polycation Form DNA Ternary Complexes for Gene Delivery
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DOI：
10.1021/bc2003378
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发表时间：
2011-09-01
影响因子：
4.7
通讯作者：
Kawakami, Hiroyoshi
中科院分区：
文献类型：
--
作者：
Asayama, Shoichiro;Nishinohara, Satoshi;Kawakami, Hiroyoshi
锌螯合聚（1-乙烯基咪唑）（PVIm-Zn）和碳水化合物配体聚阳离子，聚（L-赖氨酸）与乳糖分子（PLL-Lac）的共轭，形成了DNA三元复合物的基因传递。PLL-Lac的加入降低了PVIm-Zn/DNA负zeta电位复合物的粒径。PLL-Lac/PVIm-Zn/DNA三元复合物具有pH依赖性的PLL-Lac解离，比PVIm/DNA二元复合物介导更多的基因表达。具有细胞表面受体特异性识别的PLL-Lac/PVIm-Zn/DNA复合物在相对较低的电荷比（正/负= 2.5）下介导最高的基因表达而没有细胞毒性。这些结果表明，pH依赖性的糖配体的解离后，细胞表面受体的识别，包括物理化学和生化功能的PVIm-Zn，在基因表达中发挥了重要作用。
Zinc-chelated poly(1-vinylimidazole) (PVIm-Zn) and a carbohydrate ligand polycation, a poly(L-lysine) conjugated with lactose molecules (PLL-Lac), have formed DNA ternary complexes for gene delivery. The particle size of the PVIm-Zn/DNA complexes with negative zeta potential was decreased by the addition of the PLL-Lac. The resulting PLL-Lac/PVIm-Zn/DNA ternary complexes, which exhibited the pH-dependent dissociation of the PLL-Lac, mediated more gene expression than the PVIm/DNA binary complexes. The PLL-Lac/PVIm-Zn/DNA complexes with the specific recognition of cell surface receptors mediated the highest gene expression without cytotoxicity at a relatively lower charge ratio (positive/negative = 2.5). These results suggest that the pH-dependent dissociation of the carbohydrate ligands after the recognition of cell surface receptors, including the physicochemical and biochemical function of PVIm-Zn, played an important role in gene expression.