Light‐Responsive Supramolecular Hydrogels with Enhanced Strength via Host‐Guest Interactions for Controlled Drug Release

ABSTRACT Multifunctional hydrogels with mechanical properties, self‐healing and stimulus‐responsive capabilities are one of the key demands in the field of advanced drug delivery systems. Herein, a light‐triggered supramolecular hydrogel was designed and synthesized via a multicomponent reaction of azobenzene‐methacrylamide (Azo‐MAAm), β‐cyclodextrin (β‐CD) nanogel, and acrylic acid (AAc). The hydrogel exhibits UV‐responsive tunability due to the photo‐isomerization of the azobenzene moiety, which modulates its binding affinity with β‐CD nanogels, thereby altering the cross‐linking density and rheological properties. β‐CD nanogel form multiple cross‐linking sites with the gel matrix through their abundant surface functional groups, which significantly enhances the cross‐linking density of the polymer network, thereby effectively improving the mechanical properties of the hydrogel. Upon UV irradiation, the hydrogel undergoes a gel‐to‐sol transition, driven by the disassembly of host‐guest macro‐crosslinker complexes (β‐CD/Azo). Furthermore, the hydrogel demonstrates precise light‐controlled drug release capabilities. When loaded with rhodamine B (RhB), the hydrogel enables on‐demand release under UV light stimulation, leveraging the reversible host‐guest interactions. This light‐switchable release mechanism highlights the potential of such hydrogels in biomedical applications, including stimuli‐responsive drug delivery systems. Our findings suggest that host‐guest macro‐crosslinking provides a robust strategy for designing smart hydrogels with spatiotemporal control, broadening their utility in biotechnology and precision medicine.