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

Abstract

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.

Precise diagnosis of cardiac‐cerebral vascular diseases with magnetic resonance imaging‐based nanoprobes

“…In addition, a number of other studies are being carried out. For instance, ultrasmall calcium carbonate doped with gadolinium (Gd) coated with alendronate and trimannose were also applied for microcalcification and inflammation MR imaging [118]. Given that Ox-LDL is a characteristic component of vulnerable plaques, Li et al conjugated ASA6 (a novel scFV antibody that can bind with Ox-LDL) to NaNdF 4 @NaGdF 4 nanoparticles for imaging of atherosclerotic plaques.…”

Design and Fabrication of Environmentally Responsive Nanoparticles for the Diagnosis and Treatment of Atherosclerosis

“…(2) AS imaging using NPs: NPs can serve as contrast agents or imaging probes in various imaging techniques such as MRI, CT, and ultrasound. 34 These NPs can enhance the visualization and characterization of AP, which can aid in the diagnosis and monitoring of the disease. For example, magnetite-based magnetic NPs can be utilized to increase tissue penetration depth, provide photothermal therapy, target lesions, and aid in MRI imaging.…”