Abstract
Atherosclerosis is the leading cause of cardiovascular disease and myocardial infarction. Precise and effective plaque targeting is a major objective for therapeutic outcomes throughout various stages of atherosclerosis. Inspired by the natural recruitment of neutrophils in atherosclerotic plaques, we fabricated a simvastatin (ST)-loaded and neutrophil membrane-cloaked nanoplatform (NNPST) for enhancing localized payload delivery and atherosclerosis management. The resulting NNPST mimicked neutrophil function and significantly decreased macrophage-mediated phagocytosis to prolong its own circulation time in the blood. Compared to pristine nanoparticles (NPST) without a membrane coating, NNPST achieved better plaque targeting in ApoE-/- mice, as indicated by neutrophils actively recruited in atherosclerotic lesions. The higher plaque homing with NNPST was monitored by dynamic fluorescence/magnetic resonance (MR) dual-modality imaging. The results further showed that NNPST efficiently prevented atherosclerosis development mainly by suppressing local inflammatory macrophages, and the percentage of plaques in the entire aortic area was reduced to 4.75 ± 1.48 % following NNPST treatment. A biosafety assessment indicated that the biomimetic NNPST induced no noticeable toxicity in the body. This approach of neutrophil membrane-camouflaged nanoparticles offers new opportunities to various therapeutic agents for on-demand delivery in neutrophil-involved inflammatory diseases.