Mastering Dendrimer Self-Assembly for Efficient siRNA Delivery: From Conceptual Design to In Vivo Efficient Gene Silencing

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• 作者：Chao Chen ; Paola Posocco ; Xiaoxuan Liu ; Qiang Cheng ; Erik Laurini ; Jiehua Zhou ; Cheng Liu ; Yang Wang ; Jingjie Tang ; Valentina Dal Col ; Tianzhu Yu ; Suzanne Giorgio ; Maurizio Fermeglia ; Fanqi Qu ; Zicai Liang ; John J. Rossi ; Minghua Liu ; Palma Rocchi ; Sabrina Pricl and Ling Peng
• 刊名：Small
• 出版年：2016
• 出版时间：July 20, 2016
• 年：2016
• 卷：12
• 期：27
• 页码：3667-3676
• 全文大小：6291K
• ISSN：1613-6829

文摘

Self-assembly is a fundamental concept and a powerful approach in molecular science. However, creating functional materials with the desired properties through self-assembly remains challenging. In this work, through a combination of experimental and computational approaches, the self-assembly of small amphiphilic dendrons into nanosized supramolecular dendrimer micelles with a degree of structural definition similar to traditional covalent high-generation dendrimers is reported. It is demonstrated that, with the optimal balance of hydrophobicity and hydrophilicity, one of the self-assembled nanomicellar systems, totally devoid of toxic side effects, is able to deliver small interfering RNA and achieve effective gene silencing both in cells – including the highly refractory human hematopoietic CD34⁺ stem cells – and in vivo, thus paving the way for future biomedical implementation. This work presents a case study of the concept of generating functional supramolecular dendrimers via self-assembly. The ability of carefully designed and gauged building blocks to assemble into supramolecular structures opens new perspectives on the design of self-assembling nanosystems for complex and functional applications.