Customized peptide-encoded antibacterial silver–gold nanoclusters†

Abstract

Bacterial infections have led to serious threat to global human health owing to inevitable antibiotic resistance. Nanoenabled antimicrobials have already been successfully explored for compensating the deficiency of antibiotics. Ultra-small gold nanoclusters (AuNCs) with controllable surface chemistry are ideal nanomaterials for building antibacterial agents considering their high bacterial affinity and good membrane permeability. Peptides with facile design and synthesis are considered alternative ligands for forming peptide-stabilized AuNCs (P-AuNCs) for antibacterial performance. Herein, using three types of amino acids, namely, cysteine (Cys, C), alanine (Ala, A), and arginine (Arg, R), as components, three peptides (CA₂R, CA₂R₃, and CA₂R₅) were designed to form P/GSH-AuNCs after mixing with glutathione (GSH). Silver was introduced into P/GSH-AuNCs to synthesize silver-doped P-AuNCs (P/GSH-Ag-AuNCs). The antibacterial activity of P/GSH-Ag-AuNCs was much higher than those of the individual peptide and P/GSH-AuNCs and was enhanced with an increase in the Arg number. CA₂R₃/GSH-Ag-AuNCs, with facile purification, low toxicity and a wide antibacterial spectrum, were optimal for utilization as antibacterial agents, obtaining 0.7 µg mL⁻¹ Ag MBC for S. aureus and 0.9 µg mL⁻¹ Ag MBC for E. coli. This work can direct the design of peptide templates for integrating peptide-based nanomaterials and antibacterial application, thus building up multifarious antibacterial agents.