Ag/Fe3O4 nanocomposites penetrate and eradicate S. aureus biofilm in an in vitro chronic wound model

Abstract

Bacterial biofilms are a common cause of the persistence of chronic wounds, and continue to be an unsolved problem in infection microbiology due to their tolerance to antibiotics. Silver nanoparticles (Ag-NPs) have attracted attention as an alternative to antibiotics for treatment of wound infections, but their use is challenged by limited tissue penetration and high cytotoxicity. The aim of this study was to show that combination of Ag nanoparticles with Fe3O4 to produce Ag/Fe3O4 nanocomposites (NCs) can overcome these problems, as they penetrate and eradicate biofilms when applying a magnetic field. Ag/Fe3O4-NCs were synthesized using starch as a stabilizer and linker between Ag and Fe3O4 NPs, resulting in agglomerations of 20 nm Ag-NPs and 5 nm Fe3O4 NPs. The antibacterial activity was evaluated against an in vitro chronic wound biofilm model, and cytotoxicity was evaluated on human fibroblasts. Increasing the amount of starch during synthesis led to formation of NCs with increased antibacterial activity. In comparison to Ag-NPs, the NCs showed lower Ag+ release, less ROS production, were less cytotoxic, but nevertheless, their antimicrobial efficacy was higher. Furthermore, their efficiency against biofilm could be enhanced by applying a magnetic field, which ensured penetration of the entire biofilm. In conclusion, Ag/Fe3O4-NCs display important advantages over Ag-NPs as a potential avenue for development of novel therapeutic strategies for treatment of chronic wound infections.