The CD44/integrins interplay and the significance of receptor binding and re-presentation in the uptake of RGD-functionalized hyaluronic acid

Sihem Ouasti, Paul J. Kingham, Giorgio Terenghi, Nicola Tirelli

    Research output: Contribution to journalArticlepeer-review

    Abstract

    We have studied the interplay between two endocytic receptors for a carrier structure bearing two complementary ligands. Hyaluronic acid (HA; three different molecular weights) was functionalized with an RGD-containing peptide; this ancillary ligand allows the macromolecule to bind to α v integrins in addition to the classical HA internalization receptor (CD44). The uptake of HA-RGD and of native HA was assessed in a phagocytic cell model (J774.2 murine macrophages), studying the kinetics of internalization and its mechanistic details. Indications of a synergic binding to integrins and CD44 emerged for HA-RGD; possibly, a first binding to integrins allows for a pre-concentration of the macromolecule on the cell surface, which is then followed by its binding to CD44. The endocytic mechanism and kinetics appeared then dominated by CD44, which has a much slower turnover than integrins. In this study we have demonstrated that the knowledge of the rate-determining steps of the internalization of a carrier is necessary for assessing its performance. In this case, the presence of multiple ligands on a carrier was beneficial in some respect (e.g. in improved binding/targeting), but may not be sufficient to overcome penetration barriers that arise from slow receptor re-presentation. © 2011 Elsevier Ltd.
    Original languageEnglish
    Pages (from-to)1120-1134
    Number of pages14
    JournalBiomaterials
    Volume33
    Issue number4
    DOIs
    Publication statusPublished - Feb 2012

    Keywords

    • CD44
    • Hyaluronic acid
    • Integrin
    • Macrophages
    • RGD

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