Protein-Responsive Protein-Release of Supramolecular/polymer Hydrogel Composite Integrating Enzyme Activation Systems

Protein-responsive soft materials capable of the controlled release of drugs and proteins are promising for use in next-generation diagnosis methods and therapies. However, it is challenging to rationally design soft materials that respond to non-enzymatic proteins. Here, we describe a supramolecular/agarose hydrogel composite that can release a protein in response to a non-enzymatic protein. A non-enzymatic protein-responsive system was developed by hybridization of an enzyme-sensitive supramolecular hydrogel with a protein-triggered enzyme activation set. In situ imaging showed that the supramolecular/agarose hydrogel composite consisted of orthogonal domains of supramolecular fibers and agarose, which played distinct roles in protein entrapment and mechanical stiffness, respectively. Integrating the enzyme activation set with the composite allowed for controlled release of the embedded protein in response to the target protein.