title: The key role of the scaffold on the efficiency of dendrimer nanodrugs.
abstract: Dendrimers are well-defined macromolecules whose highly branched structure is reminiscent of many natural structures, such as trees, dendritic cells, neurons or the networks of kidneys and lungs. Nature has privileged such branched structures for increasing the efficiency of exchanges with the external medium; thus, the whole structure is of pivotal importance for these natural networks. On the contrary, it is generally believed that the properties of dendrimers are essentially related to their terminal groups, and that the internal structure plays the minor role of an 'innocent' scaffold. Here we show that such an assertion is misleading, using convergent information from biological data (human monocytes activation) and all-atom molecular dynamics simulations on seven families of dendrimers (13 compounds) that we have synthesized, possessing identical terminal groups, but different internal structures. This work demonstrates that the scaffold of nanodrugs strongly influences their properties, somewhat reminiscent of the backbone of proteins.
authors.affiliation: 1] Laboratoire de Chimie de Coordination du CNRS, UPR 8241, 205 route de Narbonne, BP 44099, 31077 Toulouse Cedex 4, France [2] Université de Toulouse, UPS, INP, LCC, F-31077 Toulouse, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Caminade
authors.affiliation: 1] Centre de Physiopathologie de Toulouse Purpan, F-31300 Toulouse, France [2] INSERM, U1043; CNRS, U5282; Université de Toulouse, UPS, Toulouse, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Fruchon
authors.affiliation: 1] Laboratoire de Chimie de Coordination du CNRS, UPR 8241, 205 route de Narbonne, BP 44099, 31077 Toulouse Cedex 4, France [2] Université de Toulouse, UPS, INP, LCC, F-31077 Toulouse, France.
authors.forename: Cédric-Olivier
authors.initials: CO
authors.lastname: Turrin
authors.affiliation: 1] Centre de Recherche en Cancérologie de Toulouse, F-31300 Toulouse, France [2] INSERM, U1037; CNRS, U5294; Université de Toulouse, UPS, Toulouse, France.
authors.forename: Mary
authors.initials: M
authors.lastname: Poupot
authors.affiliation: 1] Laboratoire de Chimie de Coordination du CNRS, UPR 8241, 205 route de Narbonne, BP 44099, 31077 Toulouse Cedex 4, France [2] Université de Toulouse, UPS, INP, LCC, F-31077 Toulouse, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Ouali
authors.affiliation: 1] Laboratoire de Chimie de Coordination du CNRS, UPR 8241, 205 route de Narbonne, BP 44099, 31077 Toulouse Cedex 4, France [2] Université de Toulouse, UPS, INP, LCC, F-31077 Toulouse, France.
authors.forename: Alexandrine
authors.initials: A
authors.lastname: Maraval
authors.affiliation: Department of Innovative Technologies, University of Applied Sciences and Arts of Southern Switzerland, Galleria 2, 6928 Manno, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Garzoni
authors.affiliation: Faculty of Science, J.E. Purkinje University, Ceske mladeze 8, 400 96 Ústí nad Labem, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Maly
authors.affiliation: Kazan State Architect and Civil Engineering University, Zelenaya 1, Kazan 420043, Russia.
authors.forename: Victor
authors.initials: V
authors.lastname: Furer
authors.affiliation: A.E. Arbuzov Institute of Organic and Physical Chemistry of Kazan Scientific Center of Russian Academy of Science, Arbuzov Str., 8, Kazan 420088, Russia.
authors.forename: Valeri
authors.initials: V
authors.lastname: Kovalenko
authors.affiliation: 1] Laboratoire de Chimie de Coordination du CNRS, UPR 8241, 205 route de Narbonne, BP 44099, 31077 Toulouse Cedex 4, France [2] Université de Toulouse, UPS, INP, LCC, F-31077 Toulouse, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Majoral
authors.affiliation: Department of Innovative Technologies, University of Applied Sciences and Arts of Southern Switzerland, Galleria 2, 6928 Manno, Switzerland.
authors.forename: Giovanni M
authors.initials: GM
authors.lastname: Pavan
authors.affiliation: 1] Centre de Physiopathologie de Toulouse Purpan, F-31300 Toulouse, France [2] INSERM, U1043; CNRS, U5282; Université de Toulouse, UPS, Toulouse, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Poupot
mesh_terms: D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D050071:Bone Density Conservation Agents / Q000737:chemistry / Q000494:pharmacology; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D004164:Diphosphonates / Q000737:chemistry / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry / Q000494:pharmacology; D011126:Polypropylenes / Q000737:chemistry / Q000494:pharmacology; D012821:Silanes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001372:Aza Compounds; D001672:Biocompatible Materials; D050071:Bone Density Conservation Agents; D050091:Dendrimers; D004164:Diphosphonates; C104700:PAMAM Starburst; D011126:Polypropylenes; D012821:Silanes; C504072:carbosilane; C443641:poly(propyleneimine); D011107:Polylysine