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Chen, Chao; Posocco, Paola; Liu, Xiaoxuan; Cheng, Qiang; Laurini, Erik; Zhou, Jiehua; Liu, Cheng; Wang, Yang; Tang, Jingjie; Col, Valentina Dal; Yu, Tianzhu; Giorgio, Suzanne; Fermeglia, Maurizio; Qu, Fanqi; Liang, Zicai; Rossi, John J.; Liu, Minghua; Rocchi, Palma; Pricl, Sabrina; Peng, Ling
Small (Weinheim an der Bergstrasse, Germany), 07/2016, Volume: 12, Issue: 27Journal Article
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. Supramolecular dendrimers created from small amphiphilic dendrons are able to mimic covalently constructed high‐generation dendrimers for siRNA delivery. An optimal balance between the hydrophobic alkyl chain length and the hydrophilic dendritic portion is crucial for self‐assembly of these amphiphilic dendrons into micellar nanostructures, and critically impacts the effectiveness of siRNA delivery and functional gene silencing.
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