Bernd M. Schmidt

We report the formation of metal‐organic cage‐crosslinked polymer hydrogels. To enable crosslinking of the cages and subsequent network formation, we used homodifunctionalized poly(ethylene glycol) (PEG) chains terminally substituted with bipyridines as ligands for the Pd 6 L 4 corners. The encapsulation of guest molecules into supramolecular self‐assembled metal‐organic cage‐crosslinked hydrogels, as well as ultrasound‐induced disassembly of the cages with release of their cargo, is presented in addition to their characterization by nuclear magnetic resonance (NMR) techniques, rheology, and comprehensive small‐angle X‐ray scattering (SAXS) experiments. The constrained geometries simulating external force (CoGEF) method and barriers using a force‐modified potential energy surface (FMPES) suggest that the cage‐opening mechanism starts with the dissociation of one pyridine ligand at around 0.5 nN. We show the efficient sonochemical activation of the hydrogels HG 3 – 6 , increasing the non‐covalent guest‐loading of completely unmodified drugs available for release by a factor of ten in comparison to non‐crosslinked, star‐shaped assemblies in solution.