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.