Atherosclerosis is a complex disease that can lead to
life-threatening
events, such as myocardial infarction and ischemic stroke. Despite
the severity of this disease, diagnosing plaque vulnerability remains
challenging due to the lack of effective diagnostic tools. Conventional
diagnostic protocols lack specificity and fail to predict the type
of atherosclerotic lesion and the risk of plaque rupture. To address
this issue, technologies are emerging, such as noninvasive medical
imaging of atherosclerotic plaque with customized nanotechnological
solutions. Modulating the biological interactions and contrast of
nanoparticles in various imaging techniques, including magnetic resonance
imaging, is possible through the careful design of their physicochemical
properties. However, few examples of comparative studies between nanoparticles
targeting different hallmarks of atherosclerosis exist to provide
information about the plaque development stage. Our work demonstrates
that Gd (III)-doped amorphous calcium carbonate nanoparticles are
an effective tool for these comparative studies due to their high
magnetic resonance contrast and physicochemical properties. In an
animal model of atherosclerosis, we compare the imaging performance
of three types of nanoparticles: bare amorphous calcium carbonate
and those functionalized with the ligands alendronate (for microcalcification
targeting) and trimannose (for inflammation targeting). Our study
provides useful insights into ligand-mediated targeted imaging of
atherosclerosis through a combination of in vivo imaging, ex vivo tissue analysis, and in vitro targeting
experiments.