Ternary Complexes with Core-Shell Bilayer for Double Level Targeted Gene Delivery: In Vitro and In Vivo Evaluation
Ternary Complexes with Core-Shell Bilayer for Double Level Targeted Gene Delivery: In Vitro and In Vivo Evaluation
复制标题
用于双水平靶向基因递送的具有核-壳双层的三元复合物：体外和体内评估
DOI：
10.1007/s11095-012-0960-9
复制
发表时间：
2013-05-01
影响因子：
3.7
通讯作者：
Zhang, Qiang
中科院分区：
文献类型：
--
作者：
Fan, Ying;Yao, Jing;Zhang, Qiang
本文报道了透明质酸（HA）/聚乙烯亚胺-地塞米松（PEI-Dex）/DNA三元核壳复合物的制备及其双靶向基因传递的研究。以PEI 1800-Dex为核心，使DNA纳米化，并使DNA内吞后能向细胞核转位;以聚阴离子HA为外冠，提高靶向递送能力，降低细胞毒性。研究了三元配合物的表征。系统评价了它们的生物学特性，包括转染效率、细胞毒性、细胞摄取和体内效应，结果表明，在所研究的配合物中，粒径约为160 nm的三元配合物的细胞毒性最低，转染效率最高。亚细胞定位研究证实，三元复合物可以促进更有效的细胞摄取和核转运的DNA比二元复合物。此外，Cy 7标记的三元复合物在静脉给药后在肿瘤中明显积聚，表明三元复合物可以辅助DNA靶向肿瘤。在体内实验中，HA/PEI 1800-Dex/DNA三元复合物显示出较好的抗炎活性，并能显著抑制荷瘤裸鼠的肿瘤生长，有望成为一种有前景的靶向基因传递系统。
Hyaluronic acid (HA)/polyethyleneimine-dexamethasone (PEI-Dex)/DNA ternary complexes with "core-shell" bilayer were developed for double level targeted gene delivery. A PEI1800-Dex, as a core, was applied to compact DNA into a nano-sized structure and facilitate the nuclear translocation of DNA after endocytosis into tumor cells, and a polyanion HA, as the outer corona, was employed to improve targeted tumor delivery and reduce cytotoxicity.PEI-Dex was synthesized and characterized by H-1 NMR. The characterizations of ternary complexes were investigated. Their biological properties, including transfection efficiency, cytotoxicity, cellular uptake and in vivo efficacy were evaluated systemically.Ternary complexes with the size of about 160 nm exhibited the lowest cytotoxicity and the highest transfection efficiency in B16F10 cells among investigated complexes. The sub-cellular localization study confirmed that ternary complexes could facilitate more efficient cell uptake and nuclear transport of DNA than binary complexes. Moreover, Cy7-labeled ternary complexes obviously accumulated in the tumor after i.v. administration, indicating that ternary complexes could assist the DNA targeting to the tumor. In in vivo studies, HA/PEI1800-Dex/DNA ternary complexes showed confirmed anti-inflammation activity, and could significantly suppress tumor growth of tumor-bearing nude mice.HA/PEI-Dex/DNA ternary complexes might be a promising targeted gene delivery system.