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Construction of core–shell tecto dendrimers based on supramolecular host–guest assembly for enhanced gene delivery
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2017-10-23 00:00:00 , DOI: 10.1039/c7tb02585h
Feng Chen 1, 2, 3, 4, 5 , Lingdan Kong 1, 2, 3, 4, 5 , Le Wang 4, 5, 6, 7 , Yu Fan 1, 2, 3, 4, 5 , Mingwu Shen 1, 2, 3, 4, 5 , Xiangyang Shi 1, 2, 3, 4, 5
Affiliation  

Design of dendrimer-based nanoarchitectures for enhanced gene delivery still remains a great challenge. Here, we report the design of core–shell tecto dendrimers using a supramolecular assembly approach for enhanced gene delivery applications. Firstly, β-cyclodextrin (CD)-modified generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers (G5-CD) and adamantine (Ad)-modified generation 3 (G3) PAMAM dendrimers (G3-Ad) both having amine termini were synthesized. Through the supramolecular recognition of CD and Ad, G5-CD/Ad-G3 core–shell tecto dendrimers with a G5 core and G3 shell were formed. The formed G5-CD/Ad-G3 core–shell tecto dendrimers with a size of 8.4 nm possess good monodispersity, well-defined three-dimensional structure, and quite low cytotoxicity. Importantly, with the abundant amines on the surface, the core–shell tecto dendrimers are able to transfect the luciferase (Luc) gene with an efficiency 20 times and 170 times higher than the G5-CD and G3-Ad dendrimers, respectively. The higher gene transfection efficiency can also be qualitatively confirmed by transfection of plasmid DNA encoding enhanced green fluorescence protein. Our results suggest that the developed G5-CD/Ad-G3 core–shell tecto dendrimers may be used as a promising vehicle for enhanced gene transfection applications.

中文翻译:

基于超分子宿主-客体组装构建核-壳tecto树状大分子,以增强基因的传递

设计基于树状聚合物的纳米结构以增强基因传递仍然是一个巨大的挑战。在这里,我们报道了使用超分子组装方法设计的核-壳结构树突状大分子,用于增强的基因传递应用。首先,β-环糊精(CD)修饰的第5代(G5)聚(酰胺基胺)(PAMAM)树状大分子(G5-CD)和金刚烷胺(Ad)修饰的第3代(G3)PAMAM树枝状大分子(G3-Ad)末端被合成。通过CD和Ad的超分子识别,形成了具有G5核和G3核的G5-CD / Ad-G3核-壳构造树状大分子。形成的G5-CD / Ad-G3核-壳tecto树状大分子的大小为8.4 nm,具有良好的单分散性,明确的三维结构和极低的细胞毒性。重要的是,由于表面上有丰富的胺,核-壳tecto树状大分子能够转染萤光素酶(Luc)基因,其效率分别比G5-CD和G3-Ad树状大分子高20倍和170倍。通过编码增强的绿色荧光蛋白的质粒DNA的转染也可以定性地证实较高的基因转染效率。我们的结果表明,已开发的G5-CD / Ad-G3核-壳tecto树状聚合物可以用作增强基因转染应用的有前途的载体。
更新日期:2017-11-08
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