Photothermally Responsive Magnetic Nanoparticles for Nitric Oxide Release to Combat Staphylococcus aureus Biofilms

Nitric oxide (NO) is an emerging and promising antimicrobial agent for treating biofilms, yet its enrichment in biofilms has become a major challenge. In this contribution, iron oxide-polydopamine (Fe3O4-PDA) core–shell nanoparticles were fabricated and then loaded with (N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine, BNN6), a NO donor, to yield a magnetic field-driven and near-infrared (NIR)-responsive NO delivery system for biofilm treatment. In a magnetic field, the nanoparticles were found to penetrate into and accumulate in the biofilms more effectively, resulting in a higher concentration of the nanoparticles in the biofilms, which upon exposure to NIR laser (808 nm) irradiation, heat up the local environment by the photothermal effect to trigger the release of more NO in a controlled manner. The combination of photothermal and NO gas therapies exhibited a synergistic antibacterial effect against Staphylococcus aureus biofilms in vitro, and the nanoparticles showed excellent antibacterial properties in vivo in the treatment of the mice wound infection model and accelerated the wound healing process. Overall, the Fe3O4-PDA–BNN6 nanoparticles realized spatial- and temporal-controlled release of NO in biofilms using NIR under a magnetic field, providing an effective antibiofilm strategy and taking the NO gas therapy one step closer to clinical application.