A hierarchical theranostic nanoagent for multimodal imaging and targeted foam cell intervention in atherosclerosis

Abstract Atherosclerosis (AS) is a leading cause of cardiovascular and cerebrovascular disease and is driven by lipid accumulation and chronic inflammation within arterial plaques. Foam cells play a central role in plaque growth and destabilization, yet their precise diagnosis and targeted regulation remain challenging. Here we present a hierarchical nanoagent that integrates multimodal imaging with selective foam cell intervention for improved AS management. The molecular probe enables near-infrared II fluorescence, photoacoustic, and magnetic resonance imaging, providing complementary information on plaque location, depth, and morphology. To achieve targeted therapy, the probe is co-encapsulated with atorvastatin using responsive nanocarriers camouflaged with macrophage membranes and equipped with a foam cell-targeting peptide. This hierarchical strategy enables precise targeting to inflamed plaques and foam cells, where controlled drug release promotes lipid efflux, reduces inflammatory signaling, and enhances plaque stabilization in female AS mouse models. This integrated imaging-guided therapeutic platform holds great promise for precise diagnosis and treatment of cardiovascular disease.