M2 Macrophage Membrane‐Camouflaged Fe3O4‐Cy7 Nanoparticles with Reduced Immunogenicity for Targeted NIR/MR Imaging of Atherosclerosis

Abstract Atherosclerosis （AS） is the primary reason behind cardiovascular diseases, leading to approximately one‐third of global deaths. Developing a novel multi‐model probe to detect AS is urgently required. Macrophages are the primary cells from which AS genesis occurs. Utilizing natural macrophage membranes coated on the surface of nanoparticles is an efficient delivery method to target plaque sites. Herein, Fe 3 O 4 ‐Cy7 nanoparticles (Fe 3 O 4 ‐Cy7 NPs), functionalized using an M2 macrophage membrane and a liposome extruder for Near‐infrared fluorescence and Magnetic resonance imaging, are synthesized. These macrophage membrane‐coated nanoparticles (Fe 3 O 4 @M2 NPs) enhance the recognition and uptake using active macrophages. Moreover, they inhibit uptake using inactive macrophages and human coronary artery endothelial cells. The macrophage membrane‐coated nanoparticles (Fe 3 O 4 @M0 NPs, Fe 3 O 4 @M1 NPs, Fe 3 O 4 @M2 NPs) can target specific sites depending on the macrophage membrane type and are related to C‐C chemofactor receptor type 2 protein content. Moreover, Fe 3 O 4 @M2 NPs demonstrate excellent biosafety in vivo after injection, showing a significantly higher Fe concentration in the blood than Fe 3 O 4 ‐Cy7 NPs. Therefore, Fe 3 O 4 @M2 NPs effectively retain the physicochemical properties of nanoparticles and depict reduced immunological response in blood circulation. These NPs mainly reveal enhanced targeting imaging capability for atherosclerotic plaque lesions.