In this paper, we synthesized a block copolymer containing pendent thioether functionalities by reversible addition–fragmentation chain transfer polymerization of a tert-butyloxycarbonyl (Boc)-l-methionine-(2-methacryloylethyl)­ester (Boc-METMA) monomer using a poly­(ethylene glycol) (PEG)-based chain transfer agent. The deprotection of Boc groups resulted in an oxidation and pH dual-responsive cationic block copolymer PEG-b-P­(METMA). The block copolymer PEG-b-P­(METMA) possessing protonable amine groups was water-soluble at pH < 6.0 and self-assembled to form spherical micelles at pH > 6.0. In the presence of H2O2, the micelles first became highly swollen with time and completely disassembled at last, demonstrating the H2O2-responsive feature because of the oxidation of hydrophobic thioether to hydrophilic sulfoxide. The anticancer drug curcumin (Cur) was entrapped in the polymeric micelles and the Cur-loaded micelles displayed a H2O2-triggered release profile as well as a pH-dependent release behavior, making PEG-b-P­(METMA) micelles promising nanocarriers for reactive oxygen species-responsive drug delivery. Taking advantage of the protonated amine groups, the cationic polyelectrolyte PEG-b-P­(METMA) formed polyion complex micelles with glucose oxidase (GOx) through electrostatic interactions at pH 5.8. By cross-linking the cores of PIC micelles with glutaraldehyde, the PIC micelles were fixed to generate stable GOx nanogels under physiological conditions. The GOx nanogels were glucose-responsive and exhibited glucose-dependent H2O2-generation activity in vitro and improved storage and thermal stability of GOx. Cur can be encapsulated in the GOx nanogels, and the Cur-loaded GOx nanogels demonstrate the glucose-responsive release profile. The GOx nanogels displayed high cytotoxicity to 4T1 cells and were effectively internalized by the cells. Therefore, these GOx nanogels have potential applications in the areas of cancer starvation and oxidation therapy.

This study reports the facile synthesis of 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...

We report the synthesis of pH‐ and enzyme‐responsive amphiphilic diblock copolymers through reversible addition‐fragmentation chain transfer polymerization of a lysine‐derived methacrylate monomer comprising p‐nitrobenzyl carbamate (pNBC) functionality using a poly(ethylene glycol)‐modified macro‐chain transfer agent. Depending on the hydrophobic block length, the diblock copolymers self‐assemble to form spherical micelles, wormlike micelles, and bilayered vesicles in the aqueous solution. The responsive behaviors of the polymeric vesicles to pH, enzyme, and light are investigated in detail. As the pH lowers to pH 5.0, the polymeric vesicles undergo a morphological transition from vesicles to spherical micelles. In the presence of nitroreductase and a cofactor NADH, the decomposition of pNBC releases the ε‐NH2 of the lysine moiety and hence induces the generation of the vesicles with crosslinked membranes at pH 7.4. Moreover, owing to the degradation of pNBC moiety under UV irradiation, the polymeric vesicles also demonstrate a photo‐responsive feature. As the irradiation time prolongs, it is observed a light‐triggered morphological transition from vesicles to wormlike micelles with network‐like structures.