The CD44/integrins interplay and the significance of receptor binding and re-presentation in the uptake of RGD-functionalized hyaluronic acid
2012 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 33, no 4, 1120-1134 p.Article in journal (Refereed) Published
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 alpha(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. (C) 2011 Elsevier Ltd. All rights reserved.
Place, publisher, year, edition, pages
2012. Vol. 33, no 4, 1120-1134 p.
Hyaluronic acid, Macrophages, CD44, Integrin, RGD
IdentifiersURN: urn:nbn:se:umu:diva-51450DOI: 10.1016/j.biomaterials.2011.10.009ISI: 000298273400013OAI: oai:DiVA.org:umu-51450DiVA: diva2:483418