Enzyme responsive supramolecular hydrogels assembled from nonionic peptide amphiphiles

Smart peptide hydrogels are of great interest for their great potential applications. Here, we report a facile approach to prepare a class of enzyme-responsive hydrogels in a scalable manner. These hydrogels self-assemble from a family of nonionic peptide amphiphiles (PAs) synthesized by sequential ring-opening polymerization (ROP) of γ-benzyl- L -glutamate N -carboxyanhydride (BLG-NCA) and L -tyrosine N -carboxyanhydride (Tyr-NCA), followed by subsequent aminolysis. These PA samples can readily form a clear hydrogel with a critical gelation concentration as low as 0.5 wt%. The incorporation of tyrosine residues offers hydrophobicity, hydrogen-bonding interaction and enzyme-responsive properties. The hydrogel-to-nanogel transition is observed under physiological conditions in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ). The obtained PA hydrogels are ideal candidates for the new generation of smart scaffolds.