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Unraveling the Uptake Mechanisms of Mannan Nanogel in Bone-Marrow-Derived Macrophages

Authors

  • Sílvia A. Ferreira,

    1. Institute for Biotechnology and Bioengineering (IBB), Centre for Biological Engineering, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal
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  • Alexandra Correia,

    1. Laboratory of Immunology, Department of Immune-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira, n.° 228, 4050-313 Porto, Portugal
    2. Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal
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  • Pedro Madureira,

    1. Laboratory of Immunology, Department of Immune-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira, n.° 228, 4050-313 Porto, Portugal
    2. Institute of Molecular and Cell Biology (IBMC), Rua do Campo Alegre 823, 4150-180 Porto, Portugal
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  • Manuel Vilanova,

    1. Laboratory of Immunology, Department of Immune-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira, n.° 228, 4050-313 Porto, Portugal
    2. Institute of Molecular and Cell Biology (IBMC), Rua do Campo Alegre 823, 4150-180 Porto, Portugal
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  • Francisco M. Gama

    Corresponding author
    1. Institute for Biotechnology and Bioengineering (IBB), Centre for Biological Engineering, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal
    • Institute for Biotechnology and Bioengineering (IBB), Centre for Biological Engineering, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
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Abstract

The mechanisms associated with the cellular internalization of nanomedicines must be carefully considered when designing drug- and vaccine-delivery systems. The cellular fate and effects of nanomedicines depend to a large extent on the cell uptake routes. A self-assembled mannan nanogel is developed as a vaccination platform for antigen and adjuvant delivery. The mannan nanogel uptake by murine bone-marrow-derived macrophages is found to be time-, concentration-, and energy-dependent, involving mannose-receptor-mediated phagocytosis and clathrin-mediated endocytosis. The nanogel is also visualized in the cytosol suggesting endolysosomal escape. These results indicate that mannan nanogel is a promising versatile carrier for intracellular delivery of vaccines or therapeutic agents.

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