Phenotype and functional analysis of human monocytes-derived dendritic cells loaded with a carbosilane dendrimer

• Published in: Biomaterials Vol. 31; no. 33; pp. 8749 - 8758
• Main Authors: Pion, Marjorie, Serramia, Maria J, Diaz, Laura, Bryszewska, Maria, Gallart, Teresa, García, Felipe, Gómez, Rafael, de la Mata, Francisco J, Muñoz-Fernandez, Maria Á
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.11.2010
• Subjects: Advanced Basic Science; Biomarkers - metabolism; Carbosilane dendrimer 2 G-NN16; Cell Death - drug effects; Cell Differentiation - drug effects; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell Movement - drug effects; Cytokines - secretion; Dendrimers - pharmacology; Dendrimers - toxicity; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dentistry; Human immunodeficiency virus; Humans; Immunomodulation; Lymphocyte Activation - drug effects; Monocytes - cytology; Nanoparticle; Peptide; Peptides - metabolism; Phenotype; Silanes - pharmacology; Silanes - toxicity; C–C motif chemokine 19 or 21; major histocompatibility complex class II; Nanoparticle; TNF; GM-CSF; Peptide; Carbosilane dendrimer 2 G-NN16; IL; iDC or mDC; Immunomodulation; immature or mature dendritic cells; phytohemagglutinin; nuclear magnetic resonance spectroscopy; prostaglandin 2; PBMC; active antiretroviral therapy; HLA-DR; poli(I:C); Tumor necrosis factor; human immunodeficiency virus; lipopolysaccharide; NMR spectroscopy; ART; Th1 or Th2; granulocyte-macrophage colony stimulating Factor; PHA; carboxyfluorescein succinimidyl ester; LPS; IFN; LDH; CBS; propidium iodide; polyinosinic polycytidylic acid; interleukin; carbosilane; peripheral blood mononuclear cells; PGE2; Dendritic cells; Lactate dehydrogenase; CFSE; interferon; human leukocyte antigen DR; CCL19 or CCL21; T cells helper 1 or 2; HIV; mAbs; PI; monoclonal antibody; MHC-II
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2010.07.093

Abstract Dendritic cells (DCs) play a major role in development of cell-mediated immunotherapy due to their unique role in linking innate and adaptive immunities. In spite of improvement in this area, strategies employing ex vivo generated DCs have shown limited efficacy in clinical trials. Dendrimers have been proposed as new carriers for drug delivery in aim to ameliorate DCs antigen loading that is a pivotal point in DCs approaches. In this study, we have investigated the phenotypic and functional characteristics of human monocytes-derived dendritic cells after HIV-derived peptides uptake in vitro . We have found that iDCs and mDCs were able to capture efficiently water soluble carbosilane (CBS) dendrimer 2 G-NN16 and did not induce changes in maturation markers levels at the DCs surface. Therefore, CBS 2 G-NN16-loaded mDCs migrated as efficiently as unloaded DCs towards CCL19 or CCL21. Furthermore, DCs viability, activation of allogenic naïve CD4 + T cells by mDCs and secretion of cytokines were not significantly changed by 2 G-NN16 loading. Summing up, our data indicate that CBS 2 G-NN16 has no negative effects on the pivotal properties of DCs in vitro . It should therefore be feasible to further develop this antigen loading strategy for clinical use in immunotherapy against viral infections.