Neutrophil Hitchhiking-Mediated Delivery of ROS-Scavenging Biomimetic Nanoparticles for Enhanced Treatment of Atherosclerosis

Abstract

Atherosclerosis (AS), a chronic inflammatory disease and a leading cause of cardiovascular morbidity and mortality worldwide, is a significant contributor to disability. Neutrophil extracellular traps (NETs) have been closely associated with the progression of AS and plaque vulnerability. However, developing a treatment strategy that specifically targets neutrophils and effectively reduces NET release at the lesion site remains a major challenge. In this study, a biomimetic nanosystem with neutrophil-targeting properties is engineered. Coating Prussian blue nanoparticles with bacterial biomimetic membranes (MPB NPs) enables specific recognition and internalization by neutrophils. By hitching onto neutrophils, the MPB NPs scavenge intracellular reactive oxygen species (ROS) and suppress NET formation at the lesion site. Importantly, MPB NPs reduce the size of atherosclerotic plaques by 3.29-fold, from 22.53% to 6.85%, stabilize the plaques, and halt their progression in atherosclerotic mouse models. These findings suggest that MPB NPs offer a promising therapeutic strategy for atherosclerosis, and provide a versatile platform for the treatment of NET-associated diseases.