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, H 2 O 2, 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(BCys 3 - co -MGlu 10 ) 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.