A Comparative Study of Ultrasmall Calcium Carbonate Nanoparticles for Targeting and Imaging Atherosclerotic Plaque

Atherosclerosis is a complex disease that can lead tolife-threateningevents, such as myocardial infarction and ischemic stroke. Despitethe severity of this disease, diagnosing plaque vulnerability remainschallenging due to the lack of effective diagnostic tools. Conventionaldiagnostic protocols lack specificity and fail to predict the typeof atherosclerotic lesion and the risk of plaque rupture. To addressthis issue, technologies are emerging, such as noninvasive medicalimaging of atherosclerotic plaque with customized nanotechnologicalsolutions. Modulating the biological interactions and contrast ofnanoparticles in various imaging techniques, including magnetic resonanceimaging, is possible through the careful design of their physicochemicalproperties. However, few examples of comparative studies between nanoparticlestargeting different hallmarks of atherosclerosis exist to provideinformation about the plaque development stage. Our work demonstratesthat Gd (III)-doped amorphous calcium carbonate nanoparticles arean effective tool for these comparative studies due to their highmagnetic resonance contrast and physicochemical properties. In ananimal model of atherosclerosis, we compare the imaging performanceof three types of nanoparticles: bare amorphous calcium carbonateand those functionalized with the ligands alendronate (for microcalcificationtargeting) and trimannose (for inflammation targeting). Our studyprovides useful insights into ligand-mediated targeted imaging ofatherosclerosis through a combination of in vivo imaging, ex vivo tissue analysis, and in vitro targetingexperiments.