Ledall, Jérémy and Fruchon, Séverine and Garzoni, Matteo and Pavan, Giovanni Maria and Caminade, Anne-Marie and Turrin, Cédric-Olivier and Blanzat, Muriel and Poupot, Rémy (2015) Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes. Nanoscale, 7 (42). pp. 17672-17684. ISSN 2040-3364
Full text not available from this repository.Abstract
Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.
| Item Type: | Scientific journal article, Newspaper article or Magazine article |
|---|---|
| Subjects: | Physical sciences > Chemistry |
| Depositing User: | Giovanni Maria Pavan |
| Date Deposited: | 22 Aug 2016 14:55 |
| Last Modified: | 22 Aug 2016 14:55 |
| URI: | http://repository.supsi.ch/id/eprint/7658 |
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