Reduction‐Sensitive Dextran Nanogels Aimed for Intracellular Delivery of Antigens |
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| Authors: | Dandan Li Neda Kordalivand Marieke F Fransen Ferry Ossendorp Koen Raemdonck Tina Vermonden Wim E Hennink Cornelus F van Nostrum |
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| Affiliation: | 1. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, CG, Utrecht, The Netherlands;2. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, ZA, Leiden, The Netherlands;3. Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Gent, Belgium |
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| Abstract: | Targeting of antigens to dendritic cells (DCs) to induce strong cellular immune response can be established by loading in a nano‐sized carrier and keeping the antigen associated with the particles until they are internalized by DCs. In the present study, a model antigen (ovalbumin, OVA) is immobilized in cationic dextran nanogels via disulfide bonds. These bonds are stable in the extracellular environment but are reduced in the cytosol of DCs due to the presence of glutathione. Reversible immobilization of OVA in the nanogels is demonstrated by the fact that hardly any release of the protein occurred at pH 7 in the absence of glutathione, whereas rapid release of OVA occurs once the nanogels are incubated in buffer with glutathione. Furthermore, these OVA conjugated nanogels show intracellular release of the antigen in DCs and boost the MHC class I antigen presentation, demonstrating the feasibility of this concept for the aimed intracellular antigen delivery. |
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| Keywords: | cationic nanogels confocal laser scanning microscopy intracellularly triggered release ovalbumine reduction |
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