Antimicrobial Potency of Fmoc-Phe-Phe Dipeptide Hydrogels with Encapsulated Porphyrin Chromophores Is a Promising Alternative in Antimicrobial Resistance

Biomolecules. 2024 Feb 16;14(2):226. doi: 10.3390/biom14020226.

Abstract

Antimicrobial resistance (AMR) poses a significant global health risk as a consequence of misuse of antibiotics. Owing to the increasing antimicrobial resistance, it became imperative to develop novel molecules and materials with antimicrobial properties. Porphyrins and metalloporphyrins are compounds which present antimicrobial properties especially after irradiation. As a consequence, porphyrinoids have recently been utilized as antimicrobial agents in antimicrobial photodynamic inactivation in bacteria and other microorganisms. Herein, we report the encapsulation of porphyrins into peptide hydrogels which serve as delivery vehicles. We selected the self-assembling Fmoc-Phe-Phe dipeptide, a potent gelator, as a scaffold due to its previously reported biocompatibility and three different water-soluble porphyrins as photosensitizers. We evaluated the structural, mechanical and in vitro degradation properties of these hydrogels, their interaction with NIH3T3 mouse skin fibroblasts, and we assessed their antimicrobial efficacy against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria. We found out that the hydrogels are cytocompatible and display antimicrobial efficiency against both strains with the zinc porphyrins being more efficient. Therefore, these hydrogels present a promising alternative for combating bacterial infections in the face of growing AMR concerns.

Keywords: antimicrobial activity; controlled release; encapsulation; hydrogels; photodynamic inactivation; porphyrins; self-assembling peptides.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents* / chemistry
  • Anti-Infective Agents* / pharmacology
  • Dipeptides / pharmacology
  • Drug Resistance, Bacterial
  • Escherichia coli
  • Fluorenes*
  • Hydrogels / pharmacology
  • Mice
  • NIH 3T3 Cells
  • Porphyrins* / chemistry
  • Porphyrins* / pharmacology
  • Staphylococcus aureus

Substances

  • Porphyrins
  • Anti-Bacterial Agents
  • fluorenyl-9-methoxycarbonyl diphenylalanine
  • Hydrogels
  • Anti-Infective Agents
  • Dipeptides
  • Fluorenes