Poster Z2 - Development of biomimetic nanoparticles for magnetic resonance imaging of atherosclerosis

Introduction: Atherosclerosis, the largest contributing factor to global mortality, is characterized by the development of fatty plaque in the vessel wall that results from maladaptive inflammation. Advancements in various imaging tools have improved patient outcomes, yet they remain far from optimal. Nanotechnology has emerged as a transformative force in material sciences and its medical applications. In this study, we have designed biomimetic nanoparticles to enhance the site-specific delivery of MR contrast agent to plaque sites. This enhancement aims to boost the effectiveness and accuracy of MR imaging in diagnosing cardiovascular diseases.

Materials and

Methods: To formulate the biomimetic nanodiagnostic tool, superparamagnetic iron oxide nanoparticles (SPION) were first encapsulated within a poly lactic-co-glycolic acid (PLGA) shell through a modified double emulsion method to form SPION–polymer nanoparticles (IPN), followed by cloaking with the plasma membrane isolated from mouse monocytes. The resulting monocyte membrane-coated IPN (MIPN) was characterized by dynamic light scattering (DLS), MR imaging, transmission electron microscopy (TEM), and western blot analysis. To assess the selective targeting, the differential uptake of MIPN by endothelial cells (EC), macrophages, and monocytes were determined via MR imaging and the quantification of iron content within the treated cells. Moreover, ex vivo and in vivo imaging of atherosclerotic mice was conducted on MRI to visualize the site-specific contrast change induced by i.v. administration of MIPN, followed by histology staining to confirm the preferential accumulation of MIPN within plaques.

Results, Conclusions, and Discussions: Our DLS results showed that IPN and MIPN maintained a 227nm and 275nm hydrodynamic diameter, respectively, while MIPN maintained a surface charge of -20mV, similar to that of the monocyte plasma membrane, all of which indicate successful cloaking of IPN with monocyte membranes. Our TEM imaging further confirmed that monocyte membranes enclosed IPN to form MIPN. Western blot analysis verified that MIPN retained monocyte membrane proteins, such as CD11b and TLR4, on their surface. Relaxometry analyses revealed that IPN and MIPN poses increased T2 relaxivity compared to SPION, indicating an ability to induce larger contrast change at lower concentrationss. Our in vitro assays demonstrated that MIPN has an enhanced cellular uptake by TNFα-activated ECs compared to IPN and SPION, as shown by a 3-fold increase in iron content and a 0.5-fold decrease in MR signal intensity. In contrast, MIPN significantly reduced the engulfment by mouse phagocytes compared to uncoated IPN, suggesting MIPN possesses the membrane features to enhance immune evasion. When administering MIPN to atherosclerotic mice, our imaging of mouse arterial segments (from descending aorta to carotid bifurcation) ex vivo showed MIPN induced notable signal decrease specifically in the atherosclerotic regions in the carotid artery while sparing lesion-free regions. More importantly, our in vivo MR imaging demonstrated strong T2* contrast change within aortic root and carotid bifurcation where plaque buildup is common, suggesting that MIPN has a strong capacity to specifically target and identify inflamed regions of the vasculature.

Our findings demonstrate that cloaking nanoparticles containing highly concentrated SPION with monocyte membranes enables effective MR imaging of atherosclerotic lesions. This suggests that MIPN could serve as a powerful diagnostic agent for monitoring plaque progression and potentially detecting other inflammatory diseases.

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