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 (H2O2). The obtained PA hydrogels are ideal candidates for the new generation of smart scaffolds.