A Gold/Silver Hybrid Nanoparticle for Treatment and Photoacoustic Imaging of Bacterial Infection.

Ag+ ions are a well-known antibacterial agent, and Ag nanoparticles act as a reservoir of these Ag+ ions for targeted therapy of bacterial infections. However, there are no tools to effectively trigger and monitor the release of Ag+ ions from Ag nanoparticles. Photoacoustic (PA) imaging is an emerging noninvasive imaging tool, and gold nanorods (AuNRs) are an excellent contrast agent for PA imaging. In this work, we developed Au/Ag hybrid nanoparticles by coating AuNRs with silver (Ag), which decreased their photoacoustic signal. The as-prepared, Ag-coated Au nanorods (Au/AgNRs) are stable under ambient conditions, but the addition of ferricyanide solution (1 mM) results in oxidative etching of the silver shell. The PA contrast is simultaneously recovered as the silver is released, and this PA signal offers noninvasive monitoring of localized release of Ag+ ions. The released Ag+ ions exhibit a strong bactericidal efficacy similar to equivalent free Ag+ ions (AgNO3), and the nanoparticles killed >99.99% of both (Gram-positive) methicillin-resistant Staphylococcus aureus (MRSA, 32 μM Ag+ equivalent) and (Gram-negative) Escherichia coli (8 μM Ag+ equivalent). The theranostic potential of these nanoparticles was demonstrated in a pilot in vivo study. Mice were inoculated with MRSA and Au/AgNRs were subcutaneously implanted followed by silver etching. There was a 730% increase in the PA signal ( p < 0.01) pre- and post-etching, and the bacterial counts in infected tissues of the treated group were reduced by 1000-fold (log CFU/g = 4.15 vs 7.75) versus the untreated control; this treatment efficacy was confirmed with histology. We further showed that these hybrid nanoparticles could release Ag+ after stimulation by reactive oxygen species including hydrogen peroxide and peroxynitrite. These hybrid Au/Ag nanoparticles are a useful theranostic agent for the photoacoustic imaging and treatment of bacterial infections.