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    Role of the interactions of soft hyaluronan nanomaterials with CD44 and supported bilayer membranes in the cellular uptake

    Year: 2021

    Journal: Colloid Surf. B-Biointerfaces, Volume 205, SEP

    Authors: Diaz-Salmeron, Raul; Michel, Jean-Philippe; Hadji, Hicheme; Gout, Evelyne; Vives, Romain R.; Ponchel, Gilles; Bouchemal, Kawthar

    Organizations: Institut Universitaire de France [ANR-17-CE09-0038-1]; ANR [ANR-10-LABX-33]; CNRS; GDR GAG [GDR 3739]; Investissements d'avenir program Glyco@Alps [ANR-15-IDEX-02]

    Keywords: Hyaluronan; Nanoparticles; Self-assemblies; Cell uptake; CD44; Artificial membranes

    Increasing valence by acting on nanomaterial morphology can enhance the ability of a ligand to specifically bind to targeted cells. Herein, we investigated cell internalization of soft hyaluronic acid (HA) nanoplatelets (NPs) that exhibit a typical hexagonal shape, flat surfaces and high aspect ratio (Gamma approximate to 12 to 20), as characterized by atomic force microscopy in hydrated conditions. Fluorescence imaging revealed that internalization of HA-NPs by a T24 tumor cell line and by macrophages was higher than native polysaccharide in a dose-dependent and timedependent manners. The ability of HA-NPs to efficiently compete with native HA assessed using Bio-layer interferometry showed that NPs had a stronger interaction with recombinant CD44 receptor compared to native HA. The results were discussed regarding physical properties of the NPs and the implication of multivalent interactions in HA binding to CD44. Experiments conducted on supported bilayer membranes with different compositions showed that non-specific interactions of NPs with lipid membranes were negligible. Our findings provide insights into intracellular drug delivery using soft HA-NPs through receptor-mediated multivalent interactions.
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