Mastering Dendrimer Self‐Assembly for Efficient siRNA Delivery: From Conceptual Design to In Vivo Efficient Gene Silencing |
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Authors: | 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 Ling Peng |
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Affiliation: | 1. Aix‐Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, Equipe Labellisée Ligue Contre le Cancer, Marseille, France;2. Aix‐Marseille Université, CNRS, Institut de Chimie Radicalaire, UMR 7273, Marseille, France;3. College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, P. R. China;4. Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), University of Trieste, Trieste, Italy;5. National Interuniversity Consortium for Material Science and Technology (INSTM), Research Unit MOSE‐DEA, University of Trieste, Trieste, Italy;6. Centre de Recherche en Cancérologie de Marseille, Inserm, UMR 1068, CNRS UMR 7258, Aix Marseille Université U105, Marseille, France;7. Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing, China;8. Department of Molecular and Cellular Biology, Beckman Research Institute, CA, USA;9. Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute, CA, USA;10. Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloids and Surfaces, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China |
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Abstract: | 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. |
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Keywords: | amphiphilic dendrons nanomicelles self‐assembly siRNA delivery supramolecular dendrimers |
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