title: Mannosylated dextran nanoparticles: a pH-sensitive system engineered for immunomodulation through mannose targeting.
abstract: Biotherapeutic delivery is a rapidly growing field in need of new materials that are easy to modify, are biocompatible, and provide for triggered release of their encapsulated cargo. Herein, we report on a particulate system made of a polysaccharide-based pH-sensitive material that can be efficiently modified to display mannose-based ligands of cell-surface receptors. These ligands are beneficial for antigen delivery, as they enhance internalization and activation of APCs, and are thus capable of modulating immune responses. When compared to unmodified particles or particles modified with a nonspecific sugar residue used in the delivery of antigens to dendritic cells (DCs), the mannosylated particles exhibited enhanced antigen presentation in the context of major histocompatibility complex (MHC) class I molecules. This represents the first demonstration of a mannosylated particulate system that enables enhanced MHC I antigen presentation by DCs in vitro. Our readily functionalized pH-sensitive material may also open new avenues in the development of optimally modulated vaccine delivery systems.
authors.affiliation: College of Chemistry, University of California-Berkeley, CA 94720-1460, United States.
authors.forename: Lina
authors.initials: L
authors.lastname: Cui
authors.forename: Joel A
authors.initials: JA
authors.lastname: Cohen
authors.forename: Kyle E
authors.initials: KE
authors.lastname: Broaders
authors.forename: Tristan T
authors.initials: TT
authors.lastname: Beaudette
authors.forename: Jean M J
authors.initials: JM
authors.lastname: Fréchet
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D002236:Carbohydrate Conformation; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D056747:Immunomodulation / Q000276:immunology*; D008024:Ligands; D008358:Mannose / Q000737:chemistry* / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000941:Antigens; D003911:Dextrans; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D011956:Receptors, Cell Surface; D008358:Mannose