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.

] Centre de Physiopathologie de Toulouse Purpan F 31300 Toulouse France [2] INSERM U1043; CNRS U5282; Université de Toulouse UPS Toulouse France

] Centre de Recherche en Cancérologie de Toulouse F 31300 Toulouse France [2] INSERM U1037; CNRS U5294; Université de Toulouse UPS Toulouse France

] 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

A E Arbuzov Institute of Organic and Physical Chemistry of Kazan Scientific Center of Russian Academy of Science Arbuzov Str 8 Kazan 420088 Russia

Department of Innovative Technologies University of Applied Sciences and Arts of Southern Switzerland Galleria 2 6928 Manno Switzerland

Faculty of Science J E Purkinje University Ceske mladeze 8 400 96 Ústí nad Labem Czech Republic

Kazan State Architect and Civil Engineering University Zelenaya 1 Kazan 420043 Russia

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