Dendrimeric bowties featuring hemispheric-selective decoration of ligands for microRNA-based therapy.
Dendrimeric bowties featuring hemispheric-selective decoration of ligands for microRNA-based therapy.
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DOI：
10.1021/bm301393z
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发表时间：
2013-01
影响因子：
6.2
通讯作者：
W. Gray;Ruo Jia Wu;Xiang Yin;Jihan Zhou;Michael E. Davis;Ying Luo
中科院分区：
文献类型：
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作者：
W. Gray;Ruo Jia Wu;Xiang Yin;Jihan Zhou;Michael E. Davis;Ying Luo
树枝状聚合物的特征在于限定数量的末端基团，其可以结合RNA或被生物活性分子官能化。如果所需的配体密度耗尽了用于结合足够RNA的末端基团的数量，则末端基团的这些竞争性使用可能产生僵局，反之亦然。需要一种新的树状聚合物平台，其保持高配体密度，同时保留足够的microRNA结合末端基团。在这里，我们提出了一个树枝状的“蝴蝶结”组成的一半致力于microRNA结合和配体介绍的另一半。我们证明了其作为转染剂的适用性，通过将miR-126通过聚精氨酸和RGD修饰的蝴蝶结传递到人血管内皮细胞（HUVEC），并评估下游对增殖和管形成的影响。我们的研究结果表明，蝴蝶结elanded所需的反应，并可能拥有优越的上级交付性能相比，nondecorated树枝状材料。因此，蝴蝶结系统提供了一种新的设计模型，用于开发用于RNAi治疗的树枝状聚合物递送载体。
Dendrimers feature a defined number of terminal groups that may bind RNA or be functionalized with bioactive molecules. These competing uses of terminal groups may create an impasse if the requisite density of ligands depletes the number of terminal groups for binding sufficient RNA, or vice versa. A novel dendrimeric platform is needed that maintains high ligand density while retaining sufficient microRNA-binding terminal groups. Here we present a dendrimeric "bowtie" consisting of one-half devoted to microRNA binding and the other half to ligand presentation. We demonstrate its suitability as a transfection agent by delivering miR-126 to human vascular endothial cells (HUVECs) via polyarginine- and RGD-modified bowties and evaluating the downstream effects on proliferation and tube formation. Our findings indicate that the bowtie elicits desired responses and may possess superior delivery properties compared to nondecorated dendrimeric materials. The bowtie system thereby provides a new design model for developing dendrimeric delivery vehicles for RNAi therapeutics.