Lipase-catalyzed synthesis of oxidation-responsive poly(ethylene glycol)-b-poly(β-thioether ester) amphiphilic block copolymers

Abstract

A series of novel oxidation-responsive amphiphilic diblock copolymers with β-thioether ester groups were synthesized via the one-step lipase-catalyzed polycondensation of methyl 3-((2-hydroxyethyl)thio)propanoate (MHETP) with monomethoxy poly(ethylene glycol) (mPEG) using immobilized lipase B from Candida antarctica (CALB) as the catalyst. The amphiphilic poly(ethylene glycol)-b-poly(β-thioether ester) (mPEG-b-PTE) diblock copolymers could self-assemble to form nanosized micelles in aqueous solution with low critical micelle concentration (CMC). The micelles were able to undergo a H₂O₂-triggered disassembly due to the oxidizable thioether groups and degradable ester groups in the hydrophobic PTE core. The oxidation-responsive behaviour of the micelles was further investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Nile Red, a hydrophobic model drug, was encapsulated into the polymeric micelles and showed fast release upon the addition of H₂O₂. Cell cytotoxicity tests indicated that the micelles had low cytotoxicity toward HeLa cells. The oxidation-insensitive poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL) diblock copolymer was also prepared for comparison. All these findings demonstrated the potential of mPEG-b-PTE diblock copolymers as a promising oxidation-responsive nanocarrier for controlled drug delivery.