Tripeptides Ghk and GhkCu-modified silver nanoparticles for enhanced antibacterial and wound healing activities

Bacterial skin infections represent a major healthcare concern that can delay healing and threaten human health. Silver nanoparticles (AgNPs) have been widely used for antimicrobial purposes; however, their high toxicity limits their applications. Therefore, there is an urgent need to develop simple and efficient therapeutic approaches for treating bacterial infections and promoting wound healing. Here, novel tripeptide (Ghk and GhkCu)-modified AgNPs were developed and subsequently evaluated their antibacterial efficacy against four pathogenic bacterial isolates, cytotoxic properties, and therapeutic effects as a topical treatment for infected wounds. Spherical GhkAgNPs and GhkCuAgNPs with average sizes of 45.92 nm and 56.82 nm exhibited potential antibacterial activity, with a MIC concentration of 8 μg/ml against S. aureus and E. coli. Both AgNPs showed superior bactericidal effects against S. aureus, with complete inhibition after 7 days of treatment. Cytotoxicity assays revealed IC₅₀ (half maximal inhibitory concentrations) values ranging from 6.75 to 6.99 µg/ml in L929 cells. GhkAgNPs displayed accelerated cell migration and facilitated healing up to 92% after 12 h. Furthermore, topical applications of GhkAgNPs and GhkCuAgNPs to S. aureus-infected wounds demonstrated enhanced in vivo wound healing efficacy compared to control groups, as evidenced by increased regenerated epidermal thickness, improved collagen deposition, and downregulation of TNF-α expression. Hence concluded that these novel tripeptides Ghk and GhkCu-modified AgNPs exhibited potent antibacterial effects and significantly promoted wound healing properties.