Abstract
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, chloroperoxidase CiVCPO and the unspecific peroxygenase rAaeUPO. Both enzymes accelerated the oxidation process, enabling the hydrogels to collapse with 10 times lower H2O2 concentrations 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.
Original language | English |
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Pages (from-to) | 3184-3192 |
Number of pages | 9 |
Journal | Biomacromolecules |
Volume | 24 |
Issue number | 7 |
DOIs | |
Publication status | Published - 2023 |