Calcium-binding nanoparticles for vascular disease

Abstract

Cardiovascular disease (CVD) including atherosclerosis is the leading cause of death worldwide. As CVDs and atherosclerosis develop, plaques begin to form in the blood vessels and become calcified. Calcification within the vasculature and atherosclerotic plaques have been correlated with rupture and consequently, acute myocardial infarction. However, current imaging methods to identify vascular calcification have limitations in determining plaque composition and structure. Nanoparticles can overcome these limitations due to their versatility and ability to incorporate a wide range of targeting and contrast agents. In this review, we summarize the current understanding of calcification in atherosclerosis, their role in instigating plaque instability, and clinical methodologies to detect and analyze vascular calcification. In addition, we highlight the potential of calcium-targeting ligands and nanoparticles to create novel calcium-detecting tools.

Keywords: Cardiovascular disease; Drug delivery; Imaging; Nanoparticle; Peptides; Vascular calcification.

Fig. 1

Plaque within the coronary artery has ruptured, causing an acute thrombus (Thr) that significantly occludes the vessel. The fibrous cap is almost nonexistent, with calcifications (black arrows) beneath the large necrotic core (NC), (a). Thrombus has formed where the thin fibrous cap (yellow arrow heads) is discontinued (b, red box). Foamy macrophages (yellow asterisks) migrate and accumulate in the thrombus, indicating inflammation (c, blue box). Reprinted with permission from Oxford University Press [4]

Fig. 2

VSMCs release EVs that initiate and propagate vascular calcification in the ECM. Upregulated levels of Runx2, annexins, Ca²⁺, and inorganic phosphate (P_i) promote calcification. Low levels of calcification inhibitor MGP is found in calcifying VSMCs

Fig. 3

Atherosclerotic plaque classifications based on virtual histology intravascular ultrasound (VH-IVUS). Plaques are categorized by intimal thickness and calcium growth (b, c, d). Calcium morphology and location can vary between types of plaques. Larger, bulk calcifications (b) have less interfacial area than spotty calcifications (c, d) causing lower circumferential stresses. The interfacial area can be assessed from the total perimeter between white and red regions in these cross-sectional images. Reprinted and adapted with permission from Wolters Kluwer Health [73, 3, 4]