Experimental and Computational Study of Injectable Iron(III)/Ultrashort Peptide Hydrogels: A Candidate for Ferroptosis-Induced Treatment of Bacterial Infections.

Fiche publication

Date publication

juin 2025

Journal

Small science

Auteurs

Membres identifiés du Cancéropôle Est :
Dr KERDJOUDJ Halima , Dr CHAN-SENG Delphine

Tous les auteurs :
Loth C, Barbault F, Guégan C, Lemaire F, Contal C, Carvalho A, Hellé S, Champion M, Kerdjoudj H, Chan-Seng D, Ploux L, Boulmedais F

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/40529877

Résumé

Injectable hydrogels are promising candidates as local drug delivery platforms for the treatment of infected wounds. Self-assembled small peptide hydrogels are of interest due to their high biocompatibility, degradability, and ease of synthesis. This study describes the formation of an injectable hydrogel based on the self-assembly of Fmoc-FFpY (Fmoc: fluorenylmethoxycarbonyl, F: phenylalanine, pY: tyrosine phosphate) triggered by electrostatic interactions in the presence of Fe ions. Stabilized by H bonding and π-π stacking, the hydrogels exhibit high mechanical stiffness with a ' (storage modulus) of ≈8000 Pa and a self-recovery up to ' ≈100 Pa. Peptide self-assembly yields β-sheets twisted into fibrillar helices of 12 nm in diameter and pitch. Molecular dynamics simulations confirm 1) the aggregation of Fmoc-FFpY in the presence of Fe and the adopted secondary structure and show that 2) the aggregated Fmoc-FFpY/Fe disrupts the bacterial membrane of and , favoring the passive entry of Fe into the pathogen. In full agreement with the simulations, the hydrogels exhibit antibacterial activity against both bacteria, likely due to the increased Fe entry into the cell, resulting in enhanced production of reactive oxygen species. This work paves the way for ferroptosis-inducing treatment of bacterial infections using injectable ultrashort peptides.