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

Nanomedicine (Lond). 2016 Oct;11(20):2631-2645. doi: 10.2217/nnm-2016-0214. Epub 2016 Sep 15.

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.

Keywords: RAFT polymerization; antigen conjugate; end-group modification; nanogels; reactive ester.

MeSH terms

  • Cross-Linking Reagents / chemistry
  • Cysteamine / chemistry
  • Drug Liberation
  • Esters / chemical synthesis
  • Esters / chemistry
  • Gels
  • Humans
  • Nanocapsules / chemistry*
  • Polyethylene Glycols / chemistry
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Serum Albumin, Bovine / chemistry
  • Sulfhydryl Compounds / chemistry
  • Sulfones / chemistry*
  • Surface Properties

Substances

  • Cross-Linking Reagents
  • Esters
  • Gels
  • Nanocapsules
  • Polymers
  • Sulfhydryl Compounds
  • Sulfones
  • Serum Albumin, Bovine
  • Polyethylene Glycols
  • divinyl sulfone
  • Cysteamine