Trapping It Softly: Ultrasoft Zirconium Metallogels for Macromolecule Entrapment and Reconfiguration

Trapping nanosized drugs in ultrasoft, shear-thinning hydrogels with large pores is of particular interest, yet a persistent challenge in nanomedicine due to the lack of hydrodynamic confinement. Engineering molecular interactions between a macromolecule and a supramolecular gel may address this shortcoming, providing a key route to develop advanced drug carriers without compromising matrix elasticity. Here, we show that ultrasoft zirconium-based metallogels are able to trap and reconfigure model nanodrugs (e.g., dextran) through complexation and hydrogen bonding. The diffusion coefficients of dextran molecules (M_w ∼ 10-2000 kDa, a ∼ 2-20 nm) in zirconium carbonate (ZC) metallogels (G' < 30 Pa) were measured by pulsed field gradient nuclear magnetic resonance (PFGNMR), which revealed the coexistence of hindered and enhanced collective diffusion regimes for the first time. This work may pave the way toward designing next generation ultrasoft drug carriers and functional templates to control biomacromolecular processes, such as protein folding.