Core/shell Protein-Reactive Nanogels Via a Combination of RAFT Polymerization and Vinyl Sulfone Postmodification

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 additionfragmentation 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.

Poly(Pentafluorophenyl Methacrylate)‐Based Nano‐Objects Developed by Photo‐PISA as Scaffolds for Post‐Polymerization Functionalization

“…PFMA‐based polymers have been extensively used to react with functional amine compounds and to introduce functional side‐groups into linear polymer molecules with high yield . Furthermore, a few examples on self‐assembly behavior of PPFMA blocks have also been reported . In this work, the PFMA activated esters have been reacted with functional amino compounds, obtaining a series of responsive nanoparticles in high yield.…”

Reactive Precursor Particles as Synthetic Platform for the Generation of Functional Nanoparticles, Nanogels, and Microgels

“…Another example of thiol–ene Michael addition for postfunctionalization of the surface as well as the interior of a colloid was reported by De Geest and co‐workers . They reported core‐crosslinked micelles with cysteine reactive vinyl sulfone moieties that can be used for protein ligation.…”

“…These vinyl sulfone moieties both in the interior as and on the surface of the micelle were used for protein ligation via thiol–ene Michael addition with the cysteine groups of the protein bovine serum albumin (BSA). Despite the sterical constraints, the vinyl sulfone moieties in the interior remained well accessible for protein conjugation . This highlights how the location of the active groups dictates the position of the introduced functionality.…”

pH-Sensitive Hydrazone-Linked Doxorubicin Nanogels via Polymeric-Activated Ester Scaffolds: Synthesis, Assembly, and In Vitro and In Vivo Evaluation in Tumor-Bearing Zebrafish

“…Our approach, depicted in Figure 1, is based on amphiphilic block copolymers consisting of a hydrophobic activated ester poly(pentafluorophenyl acrylate) 40 block and a hydrophilic poly(N,N-dimethylacrylamide) block. These block copolymers self-assemble into nanoparticles in protic apolar solvents that can be cross-linked with bisamines [41][42][43][44] . We demonstrate that the activated esters can very efficiently be converted into hydrazides by treatment with hydrazine.…”