title: Mastering Dendrimer Self-Assembly for Efficient siRNA Delivery: From Conceptual Design to In Vivo Efficient Gene Silencing.
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.
authors.affiliation: Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288, Marseille, France.|Aix-Marseille Université, CNRS, Institut de Chimie Radicalaire, UMR 7273, 13390, Marseille, France.|College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), University of Trieste, Piazzale Europa 1, 34127, Trieste, Italy.|National Interuniversity Consortium for Material Science and Technology (INSTM), Research Unit MOSE-DEA, University of Trieste, Trieste, 34127, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Posocco
authors.affiliation: Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288, Marseille, France.|Centre de Recherche en Cancérologie de Marseille, Inserm, UMR 1068, CNRS UMR 7258, Aix Marseille Université U105, Institut Paoli Calmettes, 13009, Marseille, France.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, 100871, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), University of Trieste, Piazzale Europa 1, 34127, Trieste, Italy.
authors.forename: Erik
authors.initials: E
authors.lastname: Laurini
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute, CA, 91010, USA.
authors.forename: Jiehua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288, Marseille, France.|College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, P. R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288, Marseille, France.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288, Marseille, France.
authors.forename: Jingjie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), University of Trieste, Piazzale Europa 1, 34127, Trieste, Italy.
authors.forename: Valentina Dal
authors.initials: VD
authors.lastname: Col
authors.affiliation: College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, P. R. China.
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Yu
authors.affiliation: Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288, Marseille, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Giorgio
authors.affiliation: Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), University of Trieste, Piazzale Europa 1, 34127, Trieste, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fermeglia
authors.affiliation: College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, P. R. China.
authors.forename: Fanqi
authors.initials: F
authors.lastname: Qu
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, 100871, Beijing, China.
authors.forename: Zicai
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute, CA, 91010, USA.|Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute, CA, 91010, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Rossi
authors.affiliation: Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloids and Surfaces, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Liu
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Inserm, UMR 1068, CNRS UMR 7258, Aix Marseille Université U105, Institut Paoli Calmettes, 13009, Marseille, France.
authors.forename: Palma
authors.initials: P
authors.lastname: Rocchi
authors.affiliation: Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), University of Trieste, Piazzale Europa 1, 34127, Trieste, Italy.|National Interuniversity Consortium for Material Science and Technology (INSTM), Research Unit MOSE-DEA, University of Trieste, Trieste, 34127, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pricl
authors.affiliation: Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, Equipe Labellisée Ligue Contre le Cancer, 13288, Marseille, France.
authors.forename: Ling
authors.initials: L
authors.lastname: Peng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry*; D020868:Gene Silencing / Q000502:physiology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000235:genetics / Q000628:therapy; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D050091:Dendrimers; D008823:Micelles; D034741:RNA, Small Interfering
keywords: amphiphilic dendrons; nanomicelles; self-assembly; siRNA delivery; supramolecular dendrimers