Amphoteric hyaluronic acid derivative for targeting gene delivery
Amphoteric hyaluronic acid derivative for targeting gene delivery
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DOI：
10.1016/j.biomaterials.2010.08.043
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发表时间：
2010-12-01
期刊：
影响因子：
14
通讯作者：
Sun, Xiaojing
中科院分区：
文献类型：
--
作者：
Yao, Jing;Fan, Ying;Sun, Xiaojing
针对聚乙烯亚胺（PEI）作为基因载体存在的正电荷过多、非特异性相互作用和在血液中聚集、非靶向基因传递等缺点，开发了一种两性透明质酸（HA）聚乙烯亚胺（PEI）衍生物（HAP）基因载体。通过高碘酸盐氧化的HA和PEI之间的亚胺反应合成HAP。制备了HAP/DNA复合物，并对其进行了表征。在最佳荷电比下，高分子量HA在PBS中形成的复合物的粒径约为200 nm。未观察到颗粒之间的明显聚集。HAP还显示出对DNA的高度保护免受核酸酶的侵害，更好地从复合物中解离DNA，以及更低的细胞毒性。它在HepG 2细胞中也表现出比PEI/DNA复合物更高的转染效率。在所有复合物中，特别发现HAP 50/DNA复合物是最有效的，产生与Lipofectamine/DNA lipoplexes相当的转染效率。此外，与PEI-IR 820相比，HAP-IR 820在静脉内施用后在肿瘤中明显积聚，这表明HAP可以辅助DNA靶向肿瘤。因此，HAP是一种很有前途的非病毒基因载体。(C)2010爱思唯尔有限公司版权所有。
The study aimed to develop an amphoteric hyaluronic acid (HA) derivative with polyethyleneimine (PEI) chains (HAP) for gene delivery to overcome the disadvantages of PEI as gene carrier including the cytotoxicity caused by excess of positive charge, non-special interaction and aggregation in the blood, and non-target gene delivery. The HAP was synthesized by an imine reaction between periodate-oxidized HA and PEI. The HAP/DNA complex was prepared, and its characterization was investigated. The size of complex with higher molecular weight HA in PBS was about 200 nm at optimal charge ratio. No apparent aggregation among the particles was observed. The HAPs also showed high protection of DNA from nuclease, better dissociation of DNA from the complex and lower cytotoxicity. It also exhibited higher transfection efficiency in HepG2 cells than the PEI/DNA complex. Among all complexes, the HAP50/DNA complex was especially found to be most efficient, yielding comparable transfection efficiency with that of Lipofectamine/DNA lipoplexes. Moreover, the HAP-IR820 obviously accumulated in tumor after i.v. administration as compared to the PEI-IR820, which indicated that the HAP could assist the DNA targeting to the tumor. Therefore, HAP should be a promising non-viral gene vector. (C) 2010 Elsevier Ltd. All rights reserved.