DNA Aptamer-Induced Assemblies of Peptide-Protected Silver–Gold Nanoclusters to Enhance Antibacterial Performance

Peptide-protected gold nanoclusters (P-AuNCs) were ideal candidates for constructing antibacterial agents. However, the individual P-AuNCs could only exert limited target behavior and antibacterial efficiency. Herein, CA₂R₅/GSH-AuNCs were synthesized using CA₂R₅ and glutathione (GSH), and their purification was efficiently performed by adjusting pH from 7.0 to 9.0. DNA aptamer targeting <i>Staphylococcus aureus</i> was used to assemble CA₂R₅/GSH-AuNCs to form Apt-CA₂R₅/GSH-AuNCs. After purification at pH 9.0, Apt-CA₂R₅/GSH-AuNCs were mixed with silver ions to form Apt-CA₂R₅/GSH-Ag-AuNCs. The antibacterial activity of Apt-CA₂R₅/GSH-Ag-AuNCs was much higher than that of CA₂R₅/GSH-Ag-AuNCs formed by mixing CA₂R₅/GSH-AuNCs with silver ions. The inhibitory concentration of Apt-CA₂R₅/GSH-Ag-AuNCs against <i>S. aureus</i> did not change after 40 steps of successive bacterial cultivation. The formation of bacterial biofilms was inhibited after treatment with Apt-CA₂R₅/GSH-Ag-AuNCs. The death of the bacteria was attributed to disruption of the cell membrane and change of normal metabolism. This work could provide a new concept for constructing antibacterial peptide-based nanomaterials.