Supramolecular Polymeric Hydrogels for Ultrasound‐Guided Protein Release

An ultrasound-responsive carrier for protein drugs is promising for site-specific release of proteins at disease sites in a designated time course because ultrasound readily penetrates deep into the interior of the body in a non-invasive way. However, the guideline for designing ultrasound-responsive carriers that are applicable to any protein remains to be established. Here, the aim is to develop an ultrasound-responsive material for the controlled release of a variety of proteins regardless of their charge and structure. The supramolecular polymeric hydrogel crosslinked with a host-guest interaction of β-cyclodextrin and adamantane can enclose two kinds of model proteins and site-specifically and stepwisely release them in an ultrasound-guided manner without losing their activities. Furthermore, ultrasound-guided protein delivery to living cells is achieved on model tissue consisting of cells and extracellular matrix. The results of this study provide the proof of principle that the supramolecular polymeric hydrogel is applicable as the core carrier material in an ultrasound-guided protein delivery system.