Hydrogel-to-Nanoparticle\nTransition with Immune Cell\nActivation Controlled by Dual Supramolecular Interactions

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