UV Light–Responsive Peptide‐Based Supramolecular Hydrogel for Controlled Drug Delivery

Low‐molecular‐weight self‐assembled peptides may serve as promising hydrogelators for drug delivery applications by changing their structural network in response to external stimuli. Herein, inspired by the well‐studied low‐molecular‐weight peptide hydrogelator, fluorenyl‐methoxycarbonyl‐diphenylalanine (Fmoc‐FF), a novel peptide is designed and synthesized to include an ultraviolet (UV)‐sensitive phototrigger. Similar to Fmoc‐FF, 6‐nitroveratryloxycarbonyl‐diphenylalanine (Nvoc‐FF) self‐assembles to form a 3D, self‐supporting, nanofibrous hydrogel. The Nvoc‐FF hydrogel exhibits good mechanical properties with a storage modulus of 40 kPa. UV irradiation of the Nvoc‐FF hydrogel encapsulating insulin‐fluorescein isothiocyanate (insulin‐FITC) results in the cleavage of Nvoc‐FF peptide to produce unmasked FF, thereby facilitating the degradation of the hydrogel and the release of insulin‐FITC. This release is in linear correlation to the irradiation time. In the present study, a first insight into this rigid, fibrous, light‐responsive hydrogel is provided, allowing the fabrication of a novel drug delivery system for controlled release of large molecules. A photo‐responsive peptide‐based hydrogel is designed and synthesized for drug delivery applications. 6‐Nitroveratryloxycarbonyl‐diphenylalanine (Nvoc‐FF), which self‐assembles into a rigid fibrous hydrogel, fully disassembles upon UV light irradiation in a duration‐dependent manner. Nvoc‐FF efficiently encapsulates insulin‐fluorescein isothiocyanate, which allows it to serve as a suitable vehicle for effective delivery of large active molecules.