Nane Vanparijs1,2, Lutz Nuhn1, Samantha J Paluck2, Maria Kokkinopoulou3, Ingo Lieberwirth3, Heather D Maynard2, Bruno G De Geest1. 1. Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. 2. Department of Chemistry & Biochemistry & California NanoSystems Institute, University of California, Los Angeles, 607 Charles E Young Drive East, Los Angeles, CA 90095, USA. 3. Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
Abstract
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.
AIM: A promising nanogel vaccine platform was expanded toward antigen conjugation. MATERIALS & METHODS: Block copolymers containing a reactiveester 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 reactiveester 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.
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