Abstract Body: Introduction: Contrast-enhanced magnetic resonance (MR) imaging is a powerful tool for diagnosing atherosclerosis; however, its ability to assess plaque inflammation remains limited. Here, we developed a highly sensitive, plaque-targeted biomimetic MR contrast agent for precise inflammation assessment, aiming to enhance early diagnosis and treatment monitoring in atherosclerosis.

Hypothesis: We recently developed a monocyte membrane-cloaked nanoparticle platform (MoNP) as a targeted delivery vehicle for atherosclerosis. Building on this, we hypothesize that MoNP-mediated delivery of MR contrast agents will enhance their accumulation in plaques, enabling precise spatial and temporal monitoring of inflammation status during plaque progression via MRI.

Methods: Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as T2 contrast agents for MR imaging but suffer from non-specific biodistribution and low plaque-site bioavailability, limiting their clinical utility. To address these limitations, SPIONs were encapsulated in polymeric nanoparticles (NP) via a double emulsion approach and subsequently cloaked with monocyte plasma membranes, forming MoNP-SPION. MoNP-SPION were evaluated in vitro and in mouse models using a 7-Tesla MRI.

Results: Our physicochemical characterization confirmed the successful formation of MoNP-SPION, with a hydrodynamic size of approximately 271 nm, an SPION loading capacity of 8.5%, and a high T2 relaxivity of 400 mM^-1s^-1. In vitro studies showed that MoNP-SPION exhibited significantly enhanced targeting efficiency toward TNFα-activated endothelial cells (ECs), increasing intracellular iron content 2.98-fold compared to 1.42- and 1.51-fold increases with NP-SPION and standalone SPION, respectively. MR phantom imaging further validated these findings, showing a 0.76-fold decrease in T2* signal in TNFα-activated ECs with MoNP-SPION. In vivo MR imaging of atherosclerotic mice revealed that MoNP-SPION, but not NP-SPION or SPION, induced strong T2* signal reductions in plaques at the aortic root and carotid bifurcation while sparing lesion-free areas, confirming MoNP-SPION’s capability in selective targeting and detection of plaque inflammation.

Conclusion: Our findings demonstrate that MoNP-SPION is a promising biomimetic contrast agent that enables precise MR imaging-based detection of inflammation and monitoring of plaque progression.