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

Autor:	Vanparijs N; 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., Nuhn L; Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium., Paluck SJ; Department of Chemistry & Biochemistry & California NanoSystems Institute, University of California, Los Angeles, 607 Charles E Young Drive East, Los Angeles, CA 90095, USA., Kokkinopoulou M; Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany., Lieberwirth I; Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany., Maynard HD; Department of Chemistry & Biochemistry & California NanoSystems Institute, University of California, Los Angeles, 607 Charles E Young Drive East, Los Angeles, CA 90095, USA., De Geest BG; Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Jazyk:	angličtina
Zdroj:	Nanomedicine (London, England) [Nanomedicine (Lond)] 2016 Oct; Vol. 11 (20), pp. 2631-2645. Date of Electronic Publication: 2016 Sep 15.
DOI:	10.2217/nnm-2016-0214
Abstrakt:	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. Competing Interests: Financial & competing interests disclosure N Vanparijs acknowledges BOF-UGent for a PhD scholarship. L Nuhn thanks the Alexander von Humboldt Foundation for a postdoctoral Feodor Lynen research fellowship. SJ Paluck acknowledges the NIH Chemistry Biology Interface Training Fellowship (T32 GM 008496) and UCLA Graduate Division. M Kokkinopoulou and I Lieberwirth thank the DFG SFB1066 for funding. HD Maynard acknowledges the National Institute of Health (NIH R01EB013674) for financial support. BG De Geest thanks the FWO Flanders and the Flemish Liga against Cancer for funding. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
Databáze:	MEDLINE
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