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Theoretical and experimental characterization of amino‐PEG‐phosphonate‐terminated Polyphosphorhydrazone dendrimers: Influence of size and PEG capping on cytotoxicity profiles
Authors:Aurélien Hameau  Séverine Fruchon  Christian Bijani  Alessandro Barducci  Muriel Blanzat  Rémy Poupot  Giovanni M. Pavan  Anne‐Marie Caminade  Cédric‐Olivier Turrin
Affiliation:1. CNRS, LCC (Laboratoire de Chimie de Coordination), France;2. Université de Toulouse, France;3. INSERM, U1043, CNRS 5282, Université de Toulouse, Toulouse, France;4. Laboratoire de Biophysique Statistique, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland;5. IMRCP, UMR CNRS 5623, Université Paul Sabatier, Toulouse, France;6. Department of Innovative Technologies, University of Applied Science of Southern Switzerland, Manno, Switzerland
Abstract:The synthesis of new series of PPH (poly(phosphorhydrazone)) dendrimers with amino‐PEG phosphonates or the corresponding amino‐PEG phosphonic acids as terminal groups is presented, from generations 1–3. The size of PEG‐terminated dendrimers is experimentally measured by diffusional NMR, and by means of dynamic light scattering. Classical molecular dynamics and well‐tempered metadynamics simulations are used to assess or confirm the formation of aggregates in some cases. The influence of PEG capping on the cytotoxicity profiles of the dendrimers is evaluated on human peripheral blood mononuclear cells by means of LIVE/DEAD assays, and confirms the importance of PEG capping to ensure low cytotoxicity. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 761–774
Keywords:biocompatibility  dendrimers  molecular dynamics  NMR
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