title: Nanoencapsulated budesonide in self-stratified polyurethane-polyurea nanoparticles is highly effective in inducing human tolerogenic dendritic cells.
abstract: The design of innovative strategies to selectively target cells, such antigen-presenting cells and dendritic cells, in vivo to induce immune tolerance is gaining interest and relevance for the treatment of immune-mediated diseases. A novel loaded-nanosystem strategy to generate tolerogenic dendritic cells (tol-DCs) was evaluated. Hence budesonide (BDS) was encapsulated in multiwalled polyurethane-polyurea nanoparticles (PUUa NPs-BDS) based on self-stratified polymers by hydrophobic interactions at the oil-water interface. DCs treated with encapsulated BDS presented a prominent downregulation of costimulatory molecules (CD80, CD83 and MHCII) and upregulation of inhibitory receptors. Moreover, DCs treated with these PUUa NPs-BDS also secreted large amounts of IL-10, a crucial anti-inflammatory cytokine to induce tolerance, and inhibited T lymphocyte activation in a specific manner compared to those cells generated with free BDS. These results demonstrate that PUUa NPs-BDS are a highly specific and efficient system through which to induce DCs with a tolerogenic profile. Given the capacity of PUUa NPs-BDS, this delivery system has a clear advantage for translation to in vivo studies.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Georgina
authors.initials: G
authors.lastname: Flórez-Grau
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Rocas
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Cabezón
authors.affiliation: Fundació Clínic per la Recerca Biomèdica, Barcelona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: España
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Fundació Clínic per la Recerca Biomèdica, Barcelona, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Panés
authors.affiliation: Nanobiotechnological Polymers Division, Ecopol Tech S.L., Tarragona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Rocas
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Department of Organic Chemistry, University of Barcelona, Barcelona, Spain; School of Chemistry & Physics, University of Kwazulu-Natal, Durban, South Africa; Networking Centre on Bioengineering Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain. Electronic address: albericio@ub.edu.
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.affiliation: Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. Electronic address: daniel.benitez@ciberehd.org.
authors.forename: Daniel
authors.initials: D
authors.lastname: Benítez-Ribas
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D019819:Budesonide / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007136:Immunoglobulins / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000378:metabolism; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D019819:Budesonide; D016207:Cytokines; D007136:Immunoglobulins; D016753:Interleukin-10; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D011108:Polymers; D011140:Polyurethanes; D015534:Trans-Activators; D000097802:CD83 Antigen; C508609:IL10 protein, human; C083728:MHC class II transactivator protein; C045786:polyurea
keywords: Budesonide nanoencapsulation; Cell therapies; Multiwalled nanostructures; Nanoimmunotherapy; Polyurethane-polyurea nanoparticles; Tolerogenic dendritic cells