A versatile coiled-coil tethering system for the oriented display of ligands on nanocarriers for targeted gene delivery
A versatile coiled-coil tethering system for the oriented display of ligands on nanocarriers for targeted gene delivery
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DOI：
10.1016/j.biomaterials.2012.10.047
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发表时间：
2013-01-01
期刊：
影响因子：
14
通讯作者：
Durocher, Yves
中科院分区：
文献类型：
--
作者：
Fortier, Charles;De Crescenzo, Gregory;Durocher, Yves
非病毒基因递送纳米载体的表面修饰可以提供先进的特征，例如受体靶向、内体逃逸和核输入。在这里，我们报告了一个通用的和可调的固定化方案的设计，以功能化纳米载体，以改善瞬时基因表达。我们的策略是基于线圈标记的配体和互补线圈功能化的纳米载体之间发生的特定相互作用。作为概念的证明，研究了DNA/聚乙烯亚胺聚合复合物对A431细胞的表皮生长因子受体的靶向作用。卷曲螺旋介导的表皮生长因子定向拴系引发了靶向复合物内化率的急剧增加。为了探索我们的平台的可调谐性，靶向配体的表面密度是不同的;我们的结果表明，内化率随着配体与多聚物的比例以“开关模式”的方式变化。这项工作预示了我们的卷曲螺旋平台在多重功能化中解决重组蛋白生产中瞬时基因表达瓶颈的可能途径。皇冠版权所有（C）2012由爱思唯尔有限公司出版。保留所有权利。
Surface modification of non-viral gene delivery nanocarriers may provide advanced features such as receptor targeting, endosomal escape and nuclear import. We here report the design of a versatile and tunable immobilization protocol to functionalize nanocarriers for improved transient gene expression. Our strategy is based on specific interactions occurring between a coil-tagged ligand and a complementary coil-functionalized nanocarrier. As a proof of concept, targeting of DNA/polyethylenimine polyplexes to the epidermal growth factor receptor of A431 cells was investigated. Coiled-coil-mediated oriented tethering of epidermal growth factor triggered a drastic increase of the internalization rate of the targeted polyplexes. To explore the tunability of our platform, surface density of targeting ligand was varied; our results indicated that the internalization rate varied with the ligand-to-polyplex ratio in a "switch mode" fashion. This work prefigures possible avenues for our coiled-coil platform in multiplex functionalization to address transient gene expression bottlenecks in recombinant protein production. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.