Gold Nanorods as Photoacoustic Nanoprobes to Detect Proinflammatory Macrophages and Inflammation

Key hallmarks of inflammation include proinflammatory (M1) macrophages and production of reactive oxygen species (ROS). Therefore, we developed a ROS-sensitive, photoacoustic (PA) nanoprobe capable of identifying M1 macrophages in vitro. The nanoprobe is a silica-coated gold nanorod (AuNR), which provides a stable PA signal, combined with an adsorbed polyelectrolyte-dye (poly-d-lysine (PDL)-IR775c) coating that exhibits ROS sensitivity. By monitoring the ratio between these two PA intensities, we can determine if ROS is present. Upon loading, then stimulating, macrophages toward an M1 phenotype, we observe a significant decrease in the ratio of dye/AuNR intensities relative to a nonstimulated control. Our nanoprobe is also applied to a mouse model of peripheral artery disease (PAD), where we demonstrate an ability to identify early signs of muscle inflammation before symptoms or histologic evidence. Taken together, our nanoprobe can be a powerful tool for monitoring macrophage phenotype and inflammation in vivo.