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Antigen-loaded pH-sensitive hydrogel microparticles are taken up by dendritic cells with no requirement for targeting antibodies.

ABSTRACT: Particle-based delivery of encapsulated antigens has great potential for improving vaccine constructs. In this study, we show that antigen-loaded, pH-sensitive hydrogel microparticles are taken up and presented by bone marrow-derived dendritic cells (BMDCs) in vitro and are taken up by dendritic cells (DCs) and monocytes in vivo. This uptake is irrespective of targeting antibodies. BMDCs in vitro and DCs in vivo also display upregulation of activation markers CD80 and CD86 when treated with microparticles, again with no difference in conjugated antibodies, even the agonistic CD40 antibody. We further show that these particles induce enhanced expansion of cytokine-producing CD8 T cells in response to challenge with ovalbumin-expressing vesicular stomatitis virus, in both an accelerated vaccination strategy using pre-loaded BMDCs and a traditional mouse immunization setting.

SUBMITTER: Ruff LE

PROVIDER: S-EPMC3535018 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Antigen-loaded pH-sensitive hydrogel microparticles are taken up by dendritic cells with no requirement for targeting antibodies.

Ruff Laura E LE Mahmoud Enas A EA Sankaranarayanan Jagadis J Morachis José M JM Katayama Carol D CD Corr Maripat M Hedrick Stephen M SM Almutairi Adah A

Integrative biology : quantitative biosciences from nano to macro 20130101 1

Particle-based delivery of encapsulated antigens has great potential for improving vaccine constructs. In this study, we show that antigen-loaded, pH-sensitive hydrogel microparticles are taken up and presented by bone marrow-derived dendritic cells (BMDCs) in vitro and are taken up by dendritic cells (DCs) and monocytes in vivo. This uptake is irrespective of targeting antibodies. BMDCs in vitro and DCs in vivo also display upregulation of activation markers CD80 and CD86 when treated with micr ...[more]

PMID: 23060228

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Project description:A novel and simple transcription strategy has been designed for the template-synthesis of CePO₄·xH₂O nanofibers having an improved nanofibrous morphology using a pH-sensitive nanofibrous hydrogel (glycine-alanine lipodipeptide) as structure-directing scaffold. The phosphorylated hydrogel was employed as a template to direct the mineralization of high aspect ratio nanofibrous cerium phosphate, which in-situ formed by diffusion of aqueous CeCl₃ and subsequent drying (60 °C) and annealing treatments (250, 600 and 900 °C). Dried xerogels and annealed CePO₄ powders were characterized by conventional thermal and thermogravimetric analysis (DTA/TG), and Wide-Angle X-ray powder diffraction (WAXD) and X-ray powder diffraction (XRD) techniques. A molecular packing model for the formation of the fibrous xerogel template was proposed, in accordance with results from Fourier-Transformed Infrarred (FTIR) and WAXD measurements. The morphology, crystalline structure and composition of CePO₄ nanofibers were characterized by electron microscopy techniques (Field-Emission Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy/High-Resolution Transmission Electron Microscopy (TEM/HRTEM), and Scanning Transmission Electron Microscopy working in High Angle Annular Dark-Field (STEM-HAADF)) with associated X-ray energy-dispersive detector (EDS) and Scanning Transmission Electron Microscopy-Electron Energy Loss (STEM-EELS) spectroscopies. Noteworthy, this templating approach successfully led to the formation of CePO₄·H₂O nanofibrous bundles of rather co-aligned and elongated nanofibers (10⁻20 nm thick and up to ca. 1 μm long). The formed nanofibers consisted of hexagonal (P6₂22) CePO₄ nanocrystals (at 60 and 250 °C), with a better-grown and more homogeneous fibrous morphology with respect to a reference CePO₄ prepared under similar (non-templated) conditions, and transformed into nanofibrous monoclinic monazite (P21/n) around 600 °C. The nanofibrous morphology was highly preserved after annealing at 900 °C under N₂, although collapsed under air conditions. The nanofibrous CePO₄ (as-prepared hexagonal and 900 °C-annealed monoclinic) exhibited an enhanced UV photo-luminescent emission with respect to non-fibrous homologues.

Dataset Information

Antigen-loaded pH-sensitive hydrogel microparticles are taken up by dendritic cells with no requirement for targeting antibodies.

Publications

Antigen-loaded pH-sensitive hydrogel microparticles are taken up by dendritic cells with no requirement for targeting antibodies.

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