Phenylboronic Acid-Functionalized Injectable Polypeptide Hydrogels with Responsive Drug Release

Phenylboronic acid-functionalized materials have shown great potential for versatile biomedical applications. Here, we report a facile strategy to construct phenylboronic acid-functionalized copolypeptides (mPEG-b-P(BCys-co-MGlu)) by ring-opening polymerization of S-(4-boronic acid benzyl)-l-cysteine N-carboxyanhydride (BCys NCA) and γ-methyl-l-glutamate N-carboxyanhydride (MGlu NCA) monomers. The S-(4-boronic acid benzyl)-l-cysteine (BCys) residues contain pendant phenylboronic acid groups, not only providing robust drug encapsulation capacity by virtue of N–B coordination, hydrophobic interaction, and π–π stacking but also exhibiting stimulus (GSH, H2O2, and pH)-triggered drug release. The sol-to-gel critical transition temperature and in vivo degradation could be tailored by adjusting the compositions of copolypeptides. The copolymer mPEG-b-P(BCys3-co-MGlu10) enables a sol-to-gel transition in the range of 5.6–30.3 °C at different concentrations. The prepared injectable phenylboronic acid-functionalized polypeptide hydrogel with responsive release behaviors shows great potential for local delivery applications.