Nanofibrous Peptide\nHydrogels Leveraging Histidine\nto Modulate pH-Responsive Supramolecular Assembly and Antibody Release

In this work, we investigate the\npH-responsive behavior of multidomain\npeptide (MDP) hydrogels containing histidine. Small-angle X-ray scattering\nconfirmed that MDP nanofibers sequester nonpolar residues into a hydrophobic\ncore surrounded by a shell of hydrophilic residues. MDPs with histidine\non the hydrophilic face formed nanofibers at all pH values tested,\nbut the morphology of the fibers was influenced by the protonation\nstate and the location of histidine in the MDP sequence. MDPs with\nhistidine residues within the hydrophobic face disassemble below physiological\npH and form nanofibers at higher pH. Taking advantage of their stimulus-triggered\nbehavior, an anti-PD-1 antibody was loaded into histidine MDP hydrogels\nto examine pH-dependent differences in payload delivery in vitro.\nHydrogels composed of MDPs with histidine on the hydrophilic face\ndemonstrated pH-dependent payload retention. Additionally, they showed\nsignificantly slower antibody release and reduced antibody diffusion\nrates in vitro compared to MDP hydrogels lacking histidine.