Abstract
The evolving resistance of bacteria to common antibiotics has prompted urgent demand for alternative antibacterial agents that not only control infections but are also able to prevent bacterial resistance. Silver-based nanoantibiotics are rapidly developing as promising alternatives because of their broad-spectrum antimicrobial activity, multifaceted mechanism of action and good biocompatibility. Ideally, to remain potent against a wide range of drug-resistant and anaerobic bacteria, silver-based nanoantibiotics should easily penetrate through the bacterial cell walls and actively release silver ions. However, most of the currently available silver nanomaterials are limited by their negative surface charge and the requirement of oxygen/water for the silver ion release. Here, a novel silver nanoparticle consisting of unique features including (i) ultra-small size (< 3 nm), (ii) high monodispersity, (iii) high percentage (> 50%) of silver ions content (i.e., Ag+- nanoreservoir) and (iv) polycationic surface layer was developed (referred as pAgNCs). The nanomaterial was very potent in eliminating a range of common Gram-negative and Gram-positive pathogens. Furthermore, the pAgNCs were also highly efficient in eradicating established and matured biofilms, including those composed of multiple species. The pAgNCs also showed greatly enhanced antibacterial efficacy against anaerobic bacteria such as F. nucleatum and S. sanguinis, which was attributed to the abundance of Ag+ ions in the nanoreservoir. Importantly, the pAgNCs showed a strong capacity to significantly delay the development of bacterial resistance when compared to similar-sized negatively charged AgNPs 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 broad-spectrum of pathogens and biofilms needed in many everyday life applications and industries.