title: Mannose-functionalized "pathogen-like" polyanhydride nanoparticles target C-type lectin receptors on dendritic cells.
abstract: Targeting pathogen recognition receptors on dendritic cells (DCs) offers the advantage of triggering specific signaling pathways to induce a tailored and robust immune response. In this work, we describe a novel approach to targeted antigen delivery by decorating the surface of polyanhydride nanoparticles with specific carbohydrates to provide "pathogen-like" properties that ensure nanoparticles engage C-type lectin receptors on DCs. The surface of polyanhydride nanoparticles was functionalized by covalent linkage of dimannose and lactose residues using an amine-carboxylic acid coupling reaction. Coculture of functionalized nanoparticles with bone marrow-derived DCs significantly increased cell surface expression of MHC II, the T cell costimulatory molecules CD86 and CD40, the C-type lectin receptor CIRE and the mannose receptor CD206 over the nonfunctionalized nanoparticles. Both nonfunctionalized and functionalized nanoparticles were efficiently internalized by DCs, indicating that internalization of functionalized nanoparticles was necessary but not sufficient to activate DCs. Blocking the mannose and CIRE receptors prior to the addition of functionalized nanoparticles to the culture inhibited the increased surface expression of MHC II, CD40 and CD86. Together, these data indicate that engagement of CIRE and the mannose receptor is a key mechanism by which functionalized nanoparticles activate DCs. These studies provide valuable insights into the rational design of targeted nanovaccine platforms to induce robust immune responses and improve vaccine efficacy.
authors: Department of Chemical and Biological Engineering, Iowa State University, Ames, Iowa 50011, United States.
authors: Brenda
authors: B
authors: Carrillo-Conde
authors: Eun-Ho
authors: EH
authors: Song
authors: Ana
authors: A
authors: Chavez-Santoscoy
authors: Yashdeep
authors: Y
authors: Phanse
authors: Amanda E
authors: AE
authors: Ramer-Tait
authors: Nicola L B
authors: NL
authors: Pohl
authors: Michael J
authors: MJ
authors: Wannemuehler
authors: Bryan H
authors: BH
authors: Bellaire
authors: Balaji
authors: B
authors: Narasimhan
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008358:Mannose / Q000737:chemistry*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D049388:Polyanhydrides / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism; D013499:Surface Properties; D015854:Up-Regulation; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000276:Adjuvants, Immunologic; D051940:B7-2 Antigen; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D008358:Mannose; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D049388:Polyanhydrides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C497965:Cd86 protein, mouse