Phage-mimicking antibacterial core-shell nanoparticles

The increasing frequency of nosocomial infections caused by antibiotic-resistant microorganisms concurrent with the stagnant discovery of new classes of antibiotics has made the development of new antibacterial agents a critical priority. Our approach is an antibiotic-free strategy drawing inspiration from bacteriophages to combat antibiotic-resistant bacteria. We developed a nanoparticle-based antibacterial system that structurally mimics the protein-turret distribution on the head structure of certain bacteriophages and explored a combination of different materials arranged hierarchically to inhibit bacterial growth and ultimately kill pathogenic bacteria. Here, we describe the synthesis of phage-mimicking antibacterial nanoparticles (ANPs) consisting of silver-coated gold nanospheres distributed randomly on a silica core. The silver-coating was deposited in an anisotropic fashion on the gold nanospheres. Structurally, our nanoparticles mimicked the bacteriophages of the family Microviridae by up to 88%. These phage-mimicking ANPs were tested for bactericidal efficacy against four clinically relevant nosocomial pathogens (Staphylococcus aureus USA300, Pseudomonas aeruginosa FRD1, Enterococcus faecalis, and ) and for biocompatibility with skin cells. Bacterial growth of all four bacteria was inhibited (21% to 90%) as well as delayed (by up to 5 h). The Gram-positive organisms were shown to be more sensitive to the nanoparticle treatment. Importantly, the phage-mimicking ANPs did not show any significant cytotoxic effects against human skin keratinocytes. Our results indicate the potential for phage-mimicking antimicrobial nanoparticles as a highly effective, alternative antibacterial agent, which may be suitable for co-administration with existing available formulations.