Polycationic Silver Nanoclusters Comprising Nanoreservoirs of Ag⁺Ions with High Antimicrobial and Antibiofilm Activity

Silver-based nano-antibiotics are rapidly developing as promising alternatives to conventional antibiotics. Ideally, to remain potent against a wide range of drug-resistant and anaerobic bacteria, silver-based nano-antibiotics should easily penetrate through the bacterial cell walls and actively release silver ions. In this study, highly monodispersed, ultrasmall (<3 nm), polycationic silver nanoclusters (pAgNCs) are designed and synthesized for the elimination of a range of common Gram-negative and Gram-positive pathogens and their corresponding established and matured biofilms, including those composed of multiple species. The pAgNCs also show greatly enhanced antibacterial efficacy against anaerobic bacteria such as Fusobacterium nucleatum and Streptococcus sanguinis. These results demonstrate that the cationic nature facilitates better penetration to the bacterial cell membrane while the presence of a high percentage (>50%) of silver ions (i.e., Ag+ nanoreservoirs) on the cluster surface maintains their efficiency in both aerobic and anaerobic conditions. Significantly, the pAgNCs showed a strong capacity to significantly delay the development of bacterial resistance when compared to similar-sized negatively charged silver nanoparticles or conventional antibiotics. This study demonstrates a novel design strategy that can lay the foundation for the development of future highly potent nano-antibiotics effective against a broad spectrum of pathogens and biofilms needed in many everyday life applications and industries.