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Research Article

Core/shell protein-reactive nanogels via a combination of RAFT polymerization and vinyl sulfone postmodification

    Nane Vanparijs

    Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium

    Department of Chemistry & Biochemistry & California NanoSystems Institute, University of California, Los Angeles, 607 Charles E Young Drive East, Los Angeles, CA 90095, USA

    Authors contributed equally

    Search for more papers by this author

    ,
    Lutz Nuhn

    Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium

    Authors contributed equally

    Search for more papers by this author

    ,
    Samantha J Paluck

    Department of Chemistry & Biochemistry & California NanoSystems Institute, University of California, Los Angeles, 607 Charles E Young Drive East, Los Angeles, CA 90095, USA

    ,
    Maria Kokkinopoulou

    Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany

    ,
    Ingo Lieberwirth

    Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany

    ,
    Heather D Maynard

    *Author for correspondence:

    E-mail Address: maynard@chem.ucla.edu

    Department of Chemistry & Biochemistry & California NanoSystems Institute, University of California, Los Angeles, 607 Charles E Young Drive East, Los Angeles, CA 90095, USA

    &
    Bruno G De Geest

    **Author for correspondence:

    E-mail Address: br.degeest@ugent.be

    Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium

    Published Online:https://doi.org/10.2217/nnm-2016-0214

    Aim: A promising nanogel vaccine platform was expanded toward antigen conjugation. Materials & methods: Block copolymers containing a reactive ester solvophobic block and a PEG-like solvophilic block were synthesized via reversible addition-fragmentation chain-transfer polymerization. Following self-assembly in DMSO, the esters allow for core-crosslinking and hydrophilization by amide bond formation with primary amines. Free thiols were accessed at the polymer chain ends through aminolysis of the reversible addition-fragmentation chain-transfer groups, and into the nanogel core by reactive ester conversion with cysteamine. Subsequently, free thiols were converted into vinyl sulfone moieties. Results: Despite sterical constraints, nanogel-associated vinyl sulfone moieties remained well accessible for cysteins to enforce protein conjugation successfully. Conclusion: Our present findings provide a next step toward well-defined vaccine nanoparticles that can co-deliver antigen and a molecular adjuvant.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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