Application of Engineering Efferocytosis-Mimicking Nanovesicles in Atherosclerosis Treatment via M1 Macrophages and celluar lipid metabolic reprogramming

Background and aims : Atherosclerosis is a chronic inflammatory disease driven by macrophage-mediated inflammation. This study aims to clarify the effect and mechanism of nanovesicles mimicking engineering efferocytosis on atherosclerosis, offering a multi-modal approach for atherosclerosis treatment. Methods : In this study, we investigated the therapeutic potential of Engineering efferocytosis-mimicking nanovesicles (EMNV), specifically S1P-PS-MMV and SIP-PS-MMV@SPD, in targeting and alleviating atherosclerotic lesions. Results : We demonstrated that S1P-PS-MMV could specifically target atherosclerotic plaques in a mouse model. Mechanistically, treatment with S1P-PS-MMV and S1P-PS-MMV@SPD reduced the infiltration of inflammatory cells, particularly pro-inflammatory M1 macrophages, as well as the expression of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α).Furthermore,EMNV significantly reduced the expression levels of scavenger receptors SR-A1 and CD36 involved in lipid uptake, while increasing the expression of SR-B1 stabilizing plasma cholesterol, eventually led to celluar lipid metabolic reprogramming. Conclusion: This finding demonstrates that S1P-PS-MMV and S1P-PS-MMV@SPD can effectively target atherosclerotic lesions, reduce inflammatory cell infiltration, and modulate scavenger receptor expression in macrophages, thereby alleviating plaque formation.