Article Dans Une Revue Small Science Année : 2025

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

Capucine Loth
Cécile Guégan
  • Fonction : Auteur
  • PersonId : 1007013
Christophe Contal
  • Fonction : Auteur
  • PersonId : 1377772
  • IdRef : 265696704
Alain Carvalho
  • Fonction : Auteur
  • PersonId : 1117694
  • IdRef : 258024348
Sophie Hellé
  • Fonction : Auteur
  • PersonId : 1116327
Marie Champion
Delphine Chan-Seng
Lydie Ploux

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 3+ ions. Stabilized by H bonding and π–π stacking, the hydrogels exhibit high mechanical stiffness with a G ′ (storage modulus) of ≈8000 Pa and a self‐recovery up to G ′ ≈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 3+ and the adopted secondary structure and show that 2) the aggregated Fmoc‐FFpY/Fe 3+ disrupts the bacterial membrane of Staphylococcus aureus and Pseudomonas aeruginosa , favoring the passive entry of Fe 3+ into the pathogen. In full agreement with the simulations, the hydrogels exhibit antibacterial activity against both bacteria, likely due to the increased Fe 3+ 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.

Fichier principal
Vignette du fichier
Small Science - 2025 - Loth - Experimental and Computational Study of Injectable Iron III Ultrashort Peptide Hydrogels A.pdf (4.41 Mo) Télécharger le fichier
Origine Publication financée par une institution
Licence

Dates et versions

hal-05039483 , version 1 (18-04-2025)

Licence

Identifiants

Citer

Capucine Loth, Florent Barbault, Cécile Guégan, Flora Lemaire, Christophe Contal, et al.. Experimental and Computational Study of Injectable Iron(III)/Ultrashort Peptide Hydrogels: A Candidate for Ferroptosis‐Induced Treatment of Bacterial Infections. Small Science, 2025, 5 (6), pp.2400618. ⟨10.1002/smsc.202400618⟩. ⟨hal-05039483⟩
1017 Consultations
209 Téléchargements

Altmetric

Partager

  • More