Hydrogel-to-Nanoparticle Transition with Immune Cell Activation Controlled by Dual Supramolecular Interactions

Biomolecules may undergo dynamic transitions between different aggregation states in order to adapt to the microenvironment. As a result, appropriate biofunctions can be performed only under certain states. This feature inspires exploration for constructing and regulating environmentally adaptive materials through supramolecular ways. Herein, we propose a strategy to employ a special pair of supramolecular interactions, a very strong binding between fluorescent proteins and their nanobodies together with a rather weak and dynamic binding of α-cyclodextrin and poly(ethylene glycol), to construct protein-containing polymeric hydrogel with a hydrogel-to-particle transition. The dynamic property of the originally homogeneous hydrogel was demonstrated by dilution under physiological conditions, when the complete dissociation of the hydrogel to nanoparticles was observed. This fascinating property was achieved via the very special coupling of strong protein-nanobody binding and dynamic polypseudorotaxane, which supported the hydrogel-to-particle transition and stability of the resultant particles. Such hydrogel-to-particle transition was found to efficiently promote migration of immune cells and activate them to secrete proinflammatory cytokines, indicating a bright future in immunotherapy.