Gelatin Composite Gel Particles Comprised of In-Situ Formed Zinc Oxide and Silver Nanoparticles with Enhanced Antibacterial Activities Via Enzymatic Degradation

As a globally prevalent pathogen, Staphylococcus aureus (S. aureus) poses significant challenges to disease prevention and treatment within the community. Despite the extensively established potent antibacterial activity of metal or metal oxide nanoparticles (NPs), their clinical application is impeded primarily by their unpredictable cytotoxicity. Herein, we synthesized antibacterial composite gel particles based on in-situ formed silver and zinc oxide (Ag and ZnO) NPs as antibacterial agents and gelatin for targeted drug release against S. aureus via enzymatic degradation. The as-synthesized composite gel particles exhibited enhanced antibacterial activity against S. aureus compared to other pathogenic bacteria, which could mainly be attributed to the targeted release of payloads facilitated by enzymatic degradation triggered by gelatinases in S. aureus and the well-distributed NPs in the gel network. The silver and zinc oxide NPs as well as the released ions could cause the disruption of cell membranes, bind with the deoxyribonucleic acid molecules, and release reactive oxygen species inside the cell, resulting in the bacterial cell lysis and the deoxyribonucleic acid fragmentation. The in vivo experiments showed that the Caenorhabditis elegans treated with S. aureus and Shigella flexneri were rescued by composite gel particles, evidenced by the prolonged lifespan. The Ag/ZnO/Gelatin gel particles exhibited the most potent antibacterial activity and effective protection from infection among all. This study demonstrated the selective antibacterial activities of composite gel particles on S. aureus via enzymatic degradation and highlights the importance of preparing antimicrobial agents in gelatin networks to proceed targeted release against bacteria.