Supramolecular Assemblies Based on Cucurbit[7]uril/β-Cyclodextrin-Functionalized Hyaluronic Acid and Their Biomedical Applications

With excellent biocompatibility and additional biological functions, hyaluronic acid (HA) and its derivatives have exhibited great potential in constructing versatile nano/micro materials for biological applications. The integration of HA with macrocyclic host molecules such as β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) has enabled the fabrication of sophisticated supramolecular assemblies through dynamic host-guest interactions. These HA-based supramolecular assemblies endow with CD44-targeting capability, biocompatibility, and therapeutic bioactivities with the dynamic reversibility, stimulus responsiveness, and precise molecular recognition of host-guest chemistry. This review systematically summarizes recent advances over the past five years in supramolecular assemblies based on β-CD- and CB[7]-functionalized HA across four major application domains including nanomedicines for targeted and stimuli-responsive drug delivery, dynamic hydrogels for tissue engineering and regenerative medicine, surface engineering of nanomaterials as well as living cells, and intracellular organelle manipulation for disease intervention. The design principles, key advantages, and representative examples of each application are highlighted, with particular emphasis on how the choice of macrocyclic host influences assembly stability, responsiveness, and translational potential. Finally, current challenges are discussed, and future perspectives on integrating emerging therapeutic modalities and developing intelligent, multifunctional systems are proposed.