Monocyte‐Mimetic Contrast Agent Enables Targeted and Sensitive Magnetic Resonance Imaging of Atherosclerotic Lesions

Abstract Superparamagnetic iron oxide nanoparticles (SPION) are investigated as T2 contrast agents for magnetic resonance imaging (MRI) of atherosclerosis. However, their nonspecific biodistribution and low plaque‐site bioavailability limit their translational potential. To address these challenges, monocyte membrane‐cloaked polymeric nanoparticles encapsulating SPION (MoNP‐SPION) to enhance plaque‐specific accumulation is developed. Physicochemical characterization confirmed successful MoNP‐SPION formulation, with a hydrodynamic size of ≈271 nm, SPION loading efficiency of 8.5%, and r2 relaxivity of 397.7 mM −1 s −1 . In vitro assays and phantom imaging demonstrated that MoNP‐SPION exhibited significantly enhanced targeting efficiency toward TNFα‐activated endothelial cells while minimizing uptake by monocytes and macrophages compared to its constituents. T2*‐weighted ex vivo MRI confirmed the preferential accumulation of MoNP‐SPION in atheroprone regions while sparing lesion‐free areas of the vasculature. In vivo MRI of atherosclerotic mice revealed that MoNP‐SPION, but not the uncoated counterpart or free SPION, induced strong T2*‐weighted signal reductions at the carotid bifurcations and aortic root, areas with significant plaque development, confirming its ability to enhance atherosclerosis imaging. Furthermore, toxicity assessments demonstrated the biocompatibility of MoNP‐SPION. Together, the findings highlight MoNP‐SPION as a promising biomimetic contrast agent for improving MRI‐based diagnosis of atherosclerosis, with potential applications in monitoring plaque progression and treatment outcomes.