Hydrogels that can
disintegrate upon exposure to reactive oxygen
species (ROS) have the potential for targeted drug delivery to tumor
cells. In this study, we developed a diphenylalanine (FF) derivative
with a thioether phenyl moiety attached to the N-terminus that can
form supramolecular hydrogels at neutral and mildly acidic pH. The
thioether can be oxidized by ROS to the corresponding sulfoxide, which
makes the gelator hydrolytically labile. The resulting oxidation and
hydrolysis products alter the polarity of the gelator, leading to
disassembly of the gel fibers. To enhance ROS sensitivity, we incorporated
peroxizymes in the gels, namely, chloroperoxidaseCiVCPO and the unspecific peroxygenase rAaeUPO. Both
enzymes accelerated the oxidation process, enabling the hydrogels
to collapse with 10 times lower H2O2concentrations
than those required for enzyme-free hydrogel collapse. These ROS-responsive
hydrogels could pave the way toward optimized platforms for targeted
drug delivery in the tumor microenvironment.