Linker-Regulated H2S Release from Aromatic Peptide Amphiphile Hydrogels

Controlled release is an essential requirement for delivery of hydrogen sulfide (H2S) because of its reactive nature, short half-life in biological fluids, and toxicity at high concentrations. In this context, H2S delivery via hydrogels may be beneficial as they can deliver H2S locally at the site of interest. Herein, we employed hydrogels based on aromatic peptide amphiphiles (APAs) with tunable mechanical properties to modulate the rates of H2S release. The APAs contained an aromatic S-aroylthiooxime (SATO) H2S donor attached with a linker to a short IAVEEE hexapeptide. Linker units included carbonyl, substituted O-methylenes, alkenyl, and alkyl segments with the goal of evaluating the role of linker structure on self-assembly, capacity for hydrogelation, and H2S release rate. We studied each peptide by transmission electron microscopy, circular dichroism spectroscopy, and rheology, and we measured H2S release rates from each gel, triggering SATO decomposition and release of H2S by addition of cysteine (Cys). Using an H2S-selective electrode probe as well as a turn-on fluorescent H2S probe in the presence of H9C2 cardiomyocytes, we found that the rate of H2S release from the hydrogels depended on the rate of Cys penetration into the nanofiber core with stiffer gels showing longer overall release.