Abstract

Carotid atherosclerotic plaques are a leading cause of ischemic stroke and present a major challenge for early atherosclerosis intervention. Here we engineer a biomimetic delivery platform, such as the Trojan Horse system, composed of platelet membrane and extracellular vesicles (EVs) derived from M2-like macrophages. The resulting vesicles, called platelet-extracellular vesicles (P-EVs), selectively accumulate at injured endothelium and atherosclerotic plaques and enable the co-delivery of PIM1 siRNA and Max-40279. This strategy suppresses endothelial-mesenchymal transition, reduces macrophage foam cell formation, and attenuates inflammatory responses in lesions. In mouse models of atherosclerosis, treatment with P-EVs significantly limits plaque progression. These results establish P-EVs as a targeted approach for modulating vascular inflammation and provide a potential strategy for slowing atherosclerotic plaque development.