Blanco-Gómez, ArturoBarravecchia Prado, Liliana InésVila García, AlejandroPeinador, CarlosGarcía, Marcos D.2026-05-252026-05-252026-01-06Nanoscale, 2026,18, 3365-33762040-33722040-3364https://hdl.handle.net/2183/48366[Abstract] This work reports the heterochiral tripeptide L-Phe-D-Phe-L-Phe, N-capped with vermellogen, as an ionizable pseudopeptide hydrogelator, and how the pH-responsiveness is transferred from the molecular to the nanoscale, and all the way up to the macroscale through self-assembly. In particular, the protonation of the vermellogen moiety is responsible for hydrogelation, while that of the peptide fine-tunes the matrix nanostructure and viscoelastic properties. Electron microscopy reveals the correlation of varying viscoelastic properties with the nanostructure of the hydrogel matrices. Self-assembly of the pseudopeptide undergoes a peculiar evolution from nanofibers to nanotubes. This process depends on the degree of C-terminal deprotonation, notably with the gradual increase in the internal diameter of the resulting nanotubes as the deprotonation progresses to completion. State-of-the-art characterization techniques confirm that the nanostructured gels are predominantly comprised of parallel β-sheets as primary self-assembling motifs, arranging vermellogen units in a clockwise helical pattern, which minimizes electrostatic repulsions. The evolution from nanofibers to nanotubes appears to be driven by a long-range hydrogen bonding interaction, involving the hydrazone group and the deprotonated C-terminus of adjacent β-sheets. The potential biomedical application of the gels is demonstrated through the controlled release of a model anticancer drug, and in vitro cytocompatibility assays.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articleopen access10.1039/D5NR04076K