Nine-Residue Peptide Self-Assembles in the Presence of Silver to Produce a Self-Healing, Cytocompatible, Antimicrobial Hydrogel

Abstract

Silver compounds have been used extensively for wound healing because of their antimicrobial properties, but high concentrations of silver are toxic to mammalian cells. We designed a peptide that binds silver and releases only small amounts of this ion over time, therefore overcoming the problem of silver toxicity. Silver binding was achieved through incorporation of an unnatural amino acid, 3′-pyridyl alanine (3′-PyA), into the peptide sequence. Upon the addition of silver ions, the peptide adopts a beta-sheet secondary structure and self-assembles into a strong hydrogel as characterized by rheology, circular dichroism, and transmission electron microscopy. We show that the resulting hydrogel kills Escherichia coli and Staphylococcus aureus but is not toxic to fibroblasts and could be used for wound healing. The amount of Ag­(I) released by hydrogels into the solution is less than 4% and this low amount of Ag­(I) does not change in the pH range 6–8. These studies provide an initial indication for use of the designed hydrogel as injectable, antimicrobial wound dressing.

Nanostructured Antimicrobial Peptides: Crucial Steps of Overcoming the Bottleneck for Clinics

“…Still, the AgNPs decorated by peptide-indolicidin (ILPWKWPWWPWRR) can improve the surface properties of AgNPs, significantly reducing the cytotoxicity. Additionally, except for stable conjugation between AgNPs and AMPs, D’Souza et al (2020) executed the Ag ion-controlled release system by inserting an unnatural amino acid, 3′-pyridyl alanine (3′-PyA), into the peptide sequence. The addition of the Ag ions enables peptides to form a stable hydrogel nanostructure, inducing the encapsulation of Ag(I) in an aqueous solution.…”

“…Meanwhile, the MNP–AMP is less prone to develop drug resistance due to their multiple antimicrobial actions and the damage to bacterial DNA ( Slavin et al, 2017 ). Additionally, because certain MNPs (AgNPs) possess severe toxicity in vivo , another vital reason for the combination of MNPs with AMPs is that AgNPs internalized by the bundling of AMPs decrease the binding effect on eukaryote and weaken their intrinsic cytotoxicity ( Makowski et al, 2019 ; D’Souza et al, 2020 ; Falanga et al, 2020 ). However, some studies described that the protease stability of MNP–AMP is partly improved but is invalid in the presence of high concentration protease ( Casciaro et al, 2017 ) because the MNP–AMP promotes the aggregation of AMPs on the surface of MNPs and further forms a stable nanostructure containing external AMP bundling and internal MNPs.…”

Cyanobacteria and Eukaryotic Microalgae as Emerging Sources of Antibacterial Peptides

“…An interesting research area is related with the use of metallic elements in association with peptides to enhance their activity for applications in biomedicine [196][197][198].…”

Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy

“…Strategies for combating antibiotic resistant bacteria include a number of different approaches. The scientific literature is replete with reports on novel molecules as antimicrobials including peptides, biomimetic polymers, metals, quorum signaling inhibitors, enzyme inhibitors, and non-specific biocidal molecules (Ashby et al, 2017;Mosaei and Harbottle, 2019;Kamaruzzaman et al, 2019;Rozman et al, 2019;Takahashi et al, 2017;Fordham et al, 2014;D'souza et al, 2020;Zhou et al, 2019;Shirley et al, 2018). In parallel, many groups have focused on the understanding of how bacteria develop resistance to antimicrobials.…”