Abstract

Atherosclerosis (AS) lacks the therapy of targeting and inhibiting foam cells. In this study, a biomimetic delivery system was designed utilizing monocytes as vehicles to transport reactive oxygen species (ROS)-responsive nanovehicles containing M2 macrophage secretion and ATV, thus generating reinfusion of functional monocytes (MAMS) after remodeling to treat atherosclerosis. MAMS utilized active transportation to specifically target and regulate immune responses at the focus. The findings demonstrated that MAMS effectively induced the polarization of M2 macrophages and maintained their optimal activity. MAMS exhibited significant scavenging capacity against ROS, effectively inhibited foam cell formation and promoted the efflux of lipids in vitro. Furthermore, MAMS promoted the conversion of monocytes into M2 macrophages and their migration towards foam cells. In murine models of AS, MAMS displayed significant lipid-lowering efficacy, regulated relevant enzymes, reduced foam cells and fibers, induced M2 macrophages, and regulated the proliferation of smooth muscle. The integration of this ROS-responsive material and the reinfusion of functional monocytes has resulted in a novel cell shipping administration method that exhibits a multi-faceted effect on AS treatment, including lipid reduction, inflammation resistance, antioxidant activity, targeted delivery, microenvironment modification, and immune repair. This innovative approach is poised to revolutionize the management of AS.