Elucidation of the Cellular Uptake Mechanisms of Polycationic HYDRAmers.
Fiche publication
Date publication
août 2015
Journal
Bioconjugate chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BIANCO Alberto
Tous les auteurs :
Russier J, Grillaud M, Bianco A
Lien Pubmed
Résumé
Dendrimers and dendrons appeared to potentially fulfill the requirements for being good and well-defined carriers in drug and gene delivery applications. We recently demonstrated that polycationic adamantane-based dendrons called HYDRAmers are easily internalized by both phagocytic and nonphagocytic cells in vitro. The aim of the present study was to investigate which of the different pathways of cellular internalization is involved in the cellular uptake of the first and second generation ammonium and guanidinium HYDRAmers. For this purpose, we have evaluated the internalization of fluorescently labeled HYDRAmers in both phagocytic murine macrophages and nonphagocytic human cervix epithelioid carcinoma cells in the presence of different well-known active uptake inhibitors. Our data revealed that the first and second generation HYDRAmers are internalized via different endocytic pathways based on the cellular type and on the type of functional groups present at the periphery of the dendrons. In particular, it was registered that the first generations were mainly internalized by clathrin-mediated endocytosis and macropinocytosis while the cellular internalization of the second generations was less affected by the inhibitory conditions of the endocytic pathways. These results suggest the possibility of addressing dendrimers toward specific subcellular compartments by tuning their structure properties and, in particular, the functional groups at their periphery.
Mots clés
Animals, Biological Transport, Cells, Cultured, Clathrin, metabolism, Dendrimers, chemistry, Endocytosis, physiology, Female, Flow Cytometry, Fluorescent Antibody Technique, Fluorescent Dyes, chemistry, HeLa Cells, Humans, Macrophages, cytology, Mice, Phagocytosis, physiology, Polyamines, chemistry
Référence
Bioconjug Chem. 2015 Aug 19;26(8):1484-93