Surface Ligand Chemistry of Gold Nanoclusters Determines Their Antimicrobial Ability

Surface properties of nanoparticles (NPs) could greatly influence their biomedical efficacy. This paradigm drives many NPs-based antimicrobial agents as the common belief that a more positively charged surface would favor intimate interactions with the negatively charged bacterial cell wall, leading to a higher overall antimicrobial efficacy. Surprisingly, this study shows the opposite effect when using ultrasmall gold nanoclusters (Au NCs) as a model to investigate the effect of surface properties on their antimicrobial performance. Leveraging on the molecular properties of ultrasmall Au NCs, the surface properties of thiolate-protected Au NCs could be precisely controlled at the atomic level, generating a family of Au NCs with the same number of gold atoms but different surface properties. By tuning the type and ratio of surface ligands on Au NCs, more negatively charged Au NCs would produce more reactive oxygen species (ROS), leading to a better bacterial killing efficiency. This finding is in stark contrast to the previous paradigm and suggests the complexities of the nanomaterial-cell interactions, shedding some light on the design of high-performance NP-based antimicrobial agents