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

Abstract

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.

Stimuli‐Responsive Biomolecule‐Based Hydrogels and Their Applications

“…[125] Interpeptide hydrogen bonds and cooperative pp interactions provide the driving motifs for crosslinking hydrophilic matrices that form hydrogels.D ifferent biotech- nological and biomedical applications of peptide-based hydrogels were suggested, [126] including drug delivery,sensing, immune modulation, and cancer inhibition. Thea bility to functionalize the peptide scaffold with stimuli-responsive units,f or example,p hotoisomerizable units [127] or redox groups, [128,14d,f] provide am eans to incorporate functional triggers into the hydrogel that control the stiffness properties or the supramolecular structures.I na ddition, specific recognition between low-molecular-weight ligands and proteins or glycloproteins,f or example,w ith the formation of lectinsaccharide complexes or protein-antigen-antibody complexes provide av ersatile means to crosslink proteins into soft hydrogel materials.S uch supramolecular biomaterial interactions have been broadly used to develop responsive materials with applications in tissue engineering and drug delivery. [129]…”

Preparation and applications of peptide-based injectable hydrogels

“…Optical control has unique advantages, including spatio-temporal control, indirect invasion, and low biological toxicity. 62 Thus, based on the inuence of the cell microenvironment on cell fate, the physicochemical properties of these materials can be changed in time and space by light regulation technology. This allows cell culture on the surface or inside of biological materials and provides a way to observe and guide cell physiological processes in real time, which has become a new trend in modern biological research.…”

Stimuliresponsive, auf Biomolekülen basierende Hydrogele und ihre Anwendungen

“…Lichtresponsive Hydrogele aus dem mit einem lichtempfindlichen ortho ‐Nitrobenzyl‐Derivat geschützten Dipeptid PhePhe wurden zur Stimulierung von Änderungen der Steifigkeit verwendet . So dient 6‐Nitroveratryloxycarbonyl‐PhePhe (Nvoc‐PhePhe) als Vorstufe für die Bildung eines Dipeptidhydrogels mit G′=40 kPa und G′′=1 kPa (Oszillationsversuche; Dehnung: 0.25 %; Frequenz: 1 Hz; 25 °C; Abbildung A).…”