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

Abstract

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 (AgNO), 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.

Photoacoustic Imaging: Contrast Agents and Their Biomedical Applications

“…Furthermore, gold‐based hybrid bimetallic nanorods are useful contrast agents for PA imaging as well as therapeutic agents for bacterial infections. Au/Ag hybrid nanoagents produced by coating AuNRs with Ag showed a decreased PA signal compared with the uncoated counterparts . Interestingly, Ag‐coated AuNRs were shown to be stable under ambient conditions, yet the Ag shell can be etched through the addition of a ferricyanide solution.…”

“…PA imaging has been researched for sensing of heavy‐metal ions, including copper (Cu 2+ ), methylmercury (MeHg + ), mercury(II), calcium (Ca 2+ ), lithium (Li + ), and silver (Ag + ) . For example, Chan and co‐workers developed two acoustogenic PA probes (APC‐1 and APC‐2) for the sensing of Cu 2+ .…”

Ag Nanoparticles Cluster with pH‐Triggered Reassembly in Targeting Antimicrobial Applications

“…Different from the mentioned organic antibacterial materials, as an extensively studied broad‐spectrum antimicrobial agent, [ 6 ] Ag nanoparticles (Ag NPs) released Ag + ion to damage the bacteria membrane, interfere with DNA/RNA replication, and thus wipe out the bacteria. [ 7 ] Applications of Ag NPs normally did not result in the development of antibiotics resistant bacteria, which was an advantage over organic/polymer materials.…”

A Supramolecular‐Based Dual‐Wavelength Phototherapeutic Agent with Broad‐Spectrum Antimicrobial Activity Against Drug‐Resistant Bacteria

“…Recent efforts include the use of gold nanoparticles and hybrids that, upon light irradiation, produce reactive oxygen species (ROS; photodynamic therapy, PDT) to eradicate bacteria. Another example combined gold nanorods and silver, a historically used antimicrobial agent, for the image‐guided treatment of bacterial infections . Two‐dimensional nanomaterials, such as graphene oxide (GO) and molybdenum disulfide (MoS 2 ), have also been reported as effective antimicrobial agents due to their ability to catalyze the conversion of H 2 O 2 into the hydroxyl radical (OH .…”