title: Mannosylation Allows for Synergic (CD44/C-Type Lectin) Uptake of Hyaluronic Acid Nanoparticles in Dendritic Cells, but Only upon Correct Ligand Presentation.
abstract: The selective targeting of dendritic cells (DCs) can lead to more efficacious vaccines. Here, materials have been designed for a synergic DC targeting: interacting with CD44 through the use of hyaluronic acid (HA), and with mannose-binding lectins (typical DC pattern recognition receptors) through HA mannosylation. Negatively charged, HA-displaying nanoparticles are produced via polyelectrolyte complexation of (mannosylated) HA and high- or low- molecular-weight chitosan (CS, 36 and 656 kDa). Using CS36, HA is better exposed and the particles have a higher affinity for HA receptors; this means a higher number of receptors clustered around each particle and, due to the rather limited CD44 availability, an overall lower uptake per cell. Employing Langerhans-like XS106 cells, all particles show negligible toxicity or inflammatory activation. The cellular uptake kinetics are qualitatively similar to other leukocytic models and thus considered to be CD44-dominated; the uptake increases with increasing HA mannosylation and with the use of adjuvants (LPS, mannan) for CS36/HA but not for CS656//HA particles; this indicates that the interactions with mannose-binding receptors requires a correct ligand presentation, and only in that case can they be enhanced by appropriate adjuvants. In summary, mannose-binding receptors can be used to enhance the internalization of HA-based carriers, although this positive synergy depends on the mode of ligand presentation.
authors: Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, M13 9PT, UK.
authors: Arianna
authors: A
authors: Gennari
authors: Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, M13 9PT, UK.
authors: Maria
authors: M
authors: Pelliccia
authors: NorthWest Centre of Advanced Drug Delivery (NoWCADD), Manchester Pharmacy School, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, M13 9PT, UK.
authors: Roberto
authors: R
authors: Donno
authors: Faculty of Life Sciences, The University of Manchester, Manchester, M13 9PT, UK.
authors: Ian
authors: I
authors: Kimber
authors: Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, M13 9PT, UK.|NorthWest Centre of Advanced Drug Delivery (NoWCADD), Manchester Pharmacy School, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, M13 9PT, UK.
authors: Nicola
authors: N
authors: Tirelli
mesh_terms: D000818:Animals; D002460:Cell Line; D048271:Chitosan; D003102:Colloids; D003713:Dendritic Cells / Q000378:metabolism*; D004705:Endocytosis; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D008358:Mannose / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D003102:Colloids; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D008024:Ligands; D006820:Hyaluronic Acid; D048271:Chitosan; D008358:Mannose
keywords: chitosan; dendritic cells; hyaluronic acid; lectins; mannose; nanoparticles