Tailored control and optimisation of the number of phosphonic acid termini on phosphorus-containing dendrimers for the ex-vivo activation of human monocytes.
The syntheses of a series of phosphonic acid-capped dendrimers is described. This collection is based on a unique set of dendritic structural parameters-cyclo(triphosphazene) core, benzylhydrazone branches and phosphonic acid surface-and was designed to study the influence of phosphonate (phosphonic acid) surface loading towards the activation of human monocytes ex vivo. Starting from the versatile hexachloro-cyclo(triphosphazene) N(3)P(3)Cl(6), six first-generation dendrimers were obtained, bearing one to six full branches, that lead to 4, 8, 12, 16, 20 and 24 phosphonate termini, respectively. The surface loading was also explored at the limit of dense packing by means of a first-generation dendrimer having a cyclo(tetraphosphazene) core and bearing 32 termini, and with a first-generation dendrimer based on a AB(2)/CD(5) growing pattern and bearing 60 termini. Human monocyte activation by these dendrimers confirms the requirement of the whole dendritic structure for bioactivity and identifies the dendrimer bearing four branches, thus 16 phosphonate termini, as the most bioactive.
Rolland
Olivier
O
Laboratoire de Chimie de Coordination du CNRS, UPR 8241, 205, route de Narbonne, 31077 Toulouse cedex 04, France.
Griffe
Laurent
L
Poupot
Mary
M
Maraval
Alexandrine
A
Ouali
Armelle
A
Coppel
Yannick
Y
Fournié
Jean-Jacques
JJ
Bacquet
Gérard
G
Turrin
Cédric-Olivier
CO
Caminade
Anne-Marie
AM
Majoral
Jean-Pierre
JP
Poupot
Rémy
R
D000328:Adult; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D009000:Monocytes / Q000187:drug effects*; D063065:Organophosphonates / Q000737:chemistry*; D010758:Phosphorus / Q000032:analysis*
D050091:Dendrimers; D063065:Organophosphonates; D010758:Phosphorus