Abstract
Nanomedicine can offer novel strategies in the fight against antimicrobial resistance. Nano-sized drug carriers can be used to deliver antibiotics to their target to treat infections and some nanomaterials themselves have antimicrobial properties. Here, small amphiphilic gold nanoparticles with mixed ligand surfaces have been investigated for their potential use against bacterial infections in different settings. Owing to their unique surface properties, these nanoparticles are known to directly penetrate cell membranes, instead of entering cells by energy-dependent mechanisms of endocytosis, as observed for most nanomaterials. Therefore, we aimed to explore whether this capacity could be exploited to target and eliminate bacteria. To this end, different antibiotic-loaded small amphiphilic gold nanoparticles were prepared and their antimicrobial activity against the human pathogen Staphylococcus aureus was demonstrated. Next, we tested whether the antibiotic-loaded nanoparticles could be used to treat intracellular S. aureus infections, as well as to penetrate and eradicate biofilms. In the case of intracellular infections, nanoparticle uptake was accompanied by a mild decrease in the intracellular bacterial population. In the case of biofilms, instead, the nanoparticles were able to penetrate throughout the thickness of the biofilm, rather than only reaching the upper layers, as observed for most nanomaterials. Moreover, both the amphiphilic gold nanoparticles themselves and the antibiotic-loaded variants strongly induced death of biofilm-embedded bacteria.