Abstract
Atherosclerosis remains the primary cause underlying cardiovascular diseases, however, there is no plaque-targeting pharmacotherapy clinically available. Nebivolol (NB), a third-generation beta-blocker clinically used to treat hypertension and heart failure, exerts potent antioxidative activities by inhibiting reactive oxygen species (ROS) production and scavenging ROS. Here, we developed an atherosclerotic plaque lesional macrophage-targeting nanotheranostic system that is coated with polydopamine (PDA) as a contrast agent to facilitate non-invasive photoacoustic imaging (PAI) of atherosclerotic plaques and NB as a drug to eliminate plaque ROS. In brief, mesoporous silica nanoparticles (MSNs) with interpenetrating chiral channels were coated with bioinspired PDA polymers (SPDA). PDA on the nanoparticle surface was then conjugated with hyaluronic acid (HA) to allow active targeting to atherosclerotic macrophages that overexpress CD44 (SPDA@HA). Upon loading of NB, the resulting NB/SPDA@HA nanoparticles could eliminate ROS and alleviate inflammation in activated macrophages. In addition, NB/SPDA@HA nanoparticles inhibited cell apoptosis and oxidized low density lipoprotein induced foam cell formation. Moreover, the silanols on the silica surface and the HA coating on the MSNs enable accelerated drug release from NB/SPDA@HA nanoparticles in response to the acidic and hyaluronidase-rich microenvironment in the plaque. Taken together, the dual-responsive NB/SPDA@HA nanotheranostic platform represents a promising nanomedicine for targeted atherosclerosis imaging and therapy.