Mannose-Functionalized 'Pathogen-like' Polyanhydride Nanoparticles Target C-Type Lectin Receptors on Dendritic Cells
| Autor: | Amanda E. Ramer-Tait, Brenda R. Carrillo-Conde, Michael J. Wannemuehler, Nicola L. B. Pohl, Yashdeep Phanse, Ana Vianey Chavez-Santoscoy, Balaji Narasimhan, Eun-Ho Song, Bryan H. Bellaire |
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| Rok vydání: | 2011 |
| Předmět: |
Surface Properties
media_common.quotation_subject T cell Pharmaceutical Science Mannose Bone Marrow Cells Receptors Cell Surface chemical and pharmacologic phenomena Mice chemistry.chemical_compound Adjuvants Immunologic C-type lectin Polyanhydrides Drug Discovery medicine Animals Lectins C-Type CD40 Antigens Particle Size Receptor Internalization Cells Cultured media_common CD86 Histocompatibility Antigens Class II Dendritic Cells Up-Regulation Cell biology Mice Inbred C57BL Mannose-Binding Lectins medicine.anatomical_structure Biochemistry chemistry Cytokines Nanoparticles Molecular Medicine B7-2 Antigen Signal transduction Cell Adhesion Molecules Mannose Receptor Mannose receptor |
| Zdroj: | Molecular Pharmaceutics. 8:1877-1886 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/mp200213r |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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