Targeting macrophages with multifunctional nanoparticles to detect and prevent atherosclerotic cardiovascular disease.

Despite the emergence of novel diagnostic, pharmacological, interventional and prevention strategies, atherosclerotic cardiovascular disease remains a significant cause of morbidity and mortality. Nanoparticle-based platforms encompass diverse imaging, delivery and pharmacological properties that provide novel opportunities for refining diagnostic and therapeutic interventions for atherosclerosis at the cellular and molecular level. Macrophages play a critical role in atherosclerosis and therefore represent an important disease-related diagnostic and therapeutic target, especially given their inherent ability for passive and active nanoparticle uptake. In this review, we discuss an array of inorganic, carbon-based and lipid-based nanoparticles that provide magnetic, radiographic and fluorescent imaging capabilities for a range of highly promising research and clinical applications in atherosclerosis. We discuss the design of nanoparticles that target a range of macrophage-related functions such as lipoprotein oxidation, cholesterol efflux, vascular inflammation and defective efferocytosis. We also provide examples of nanoparticle systems that were developed for other pathologies such as cancer and highlight their potential for repurposing in cardiovascular disease. Finally, we discuss the current state of play and the future of theranostic nanoparticles. Whilst this is not without its challenges, the array of multifunctional capabilities that are possible in nanoparticle design ensures they will be part of the next frontier of exciting new therapies that simultaneously improve the accuracy of plaque diagnosis and more effectively reduce atherosclerosis with limited side effects.