Oxidation and ATP dual-responsive block copolymer containing tertiary sulfoniums: self-assembly, protein complexation and triggered release

Abstract

This study reports the facile synthesis of a phenylboronic acid-functionalized block copolymer containing tertiary sulfoniums via the combination of reversible addition–fragmentation chain transfer polymerization of a methionine-derived methacrylate monomer and the alkylation of thioether. The block copolymer self-assembled to form positively charged spherical micelles in aqueous media. Because of the deboronation and subsequent benzyl 1,6-elimination reaction in the presence of H₂O₂, the micelles displayed an oxidation-responsive feature. Triggered by H₂O₂, the micelles underwent an expansion, and the surface charge decreased due to the transformation of cationic sulfoniums to neutral sulfurs. Moreover, the micelles can interact with adenosine triphosphate (ATP) via the formation of reversible boronates and electrostatic interactions. In the presence of ATP, the block copolymer micelles spontaneously contracted to small aggregates of ATP/copolymer complexes. Taking advantage of the cationic sulfoniums, the block copolymer co-assembled with negatively charged bovine serum albumin (BSA) to fabricate protein-entrapped biohybrid micelles, driven by multiple electrostatic interactions. BSA in the micelles retained 94% of the native BSA bioactivity. Triggered by H₂O₂, the BSA-entrapped micelles underwent destruction because of the charge conversion of sulfonium cations to neutral sulfurs. The BSA-entrapped micelles have good biocompatibility and demonstrate an H₂O₂ and ATP dual-responsive release profile.