Abstract

Nanotechnology could improve our understanding of the pathophysiology of atherosclerosis and contribute to the development of novel diagnostic and therapeutic strategies to further reduce the risk of cardiovascular disease. Macrophages have key roles in atherosclerosis progression and, therefore, macrophage-associated pathological processes are important targets for both diagnostic imaging and novel therapies for atherosclerosis. In this Review, we highlight efforts in the past two decades to develop imaging techniques and to therapeutically manipulate macrophages in atherosclerotic plaques with the use of rationally designed nanoparticles. We review the latest progress in nanoparticle-based imaging modalities that can specifically target macrophages. Using novel molecular imaging technology, these modalities enable the identification of advanced atherosclerotic plaques and the assessment of the therapeutic efficacy of medical interventions. Additionally, we provide novel perspectives on how macrophage-targeting nanoparticles can deliver a broad range of therapeutic payloads to atherosclerotic lesions. These nanoparticles can suppress pro-atherogenic macrophage processes, leading to improved resolution of inflammation and stabilization of plaques. Finally, we propose future opportunities for novel diagnostic and therapeutic strategies and provide solutions to challenges in this area for the purpose of accelerating the clinical translation of nanomedicine for the treatment of atherosclerotic vascular disease.

Highlights

  • Abstract | Nanotechnology could improve our understanding of the pathophysiology of atherosclerosis and contribute to the development of novel diagnostic and therapeutic strategies to further reduce the risk of cardiovascular disease

  • Apolipoprotein B-containing lipoproteins Cholesterol-rich lipoproteins, such as LDL and chylomicron remnants, that have a crucial role in atherogenesis

  • The cholesterol and oxidized phospholipids in these lipoproteins induce the activation of endothelial cells, which subsequently recruit monocytes into the subendothelial space[4,5]

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Summary

Key points

Because macrophages have key roles in atherosclerosis progression, macrophagemediated pro-atherosclerotic processes are important targets for both diagnostic imaging and novel therapies for atherosclerosis. Targeted nanotherapeutics that can modulate plaque macrophage functions by the activation or suppression of specific signalling pathways have shown great promise in preclinical models by improving therapeutic efficacy and reducing off-target and systemic adverse effects. Targeted nanoparticles have been designed to improve the delivery of imaging agents and therapeutics to inflammatory macrophages in atherosclerotic plaques. In this Review, we provide a fresh perspective on atherosclerosis nanomedicine. We discuss how the convergence of nanotechnology and a deeper understanding of the pro-atherosclerotic mechanisms mediated by macro­ phages in atherosclerotic plaques could drive advances in cardiovascular disease diagnosis and therapy. Gained over the past decades, combined with the success of nanomedicines in cancer therapy, will accelerate their future clinical translation for cardiovascular disease

Macrophage biology in atherosclerosis
Journey of nanomedicines to macrophages
Cholesterol crystal
Nanoparticles for diagnostic imaging
Evaluation of novel therapies
Nanotherapeutics in atherosclerosis
Inhibition of foam cell formation
Polymeric nanoparticles
PLGA nanoparticles Pioglitazone
Macrophage apoptosis
Promotion of cholesterol efflux from macrophages
Challenges and perspectives
Macrophage Lumen
Study pharmaceutical objectives ingredients
Paclitaxel nanoparticles
Gold nanoparticles
No regression of coronary atherosclerosis
Plaqueaccumulated liposomal prednisolone had no antiinflammatory effect
USPIO nanoparticles
Differences in Plaques in
Incidentally found SPIO nanoparticle uptake in aortic and arterial wall
Conclusions
Published online xx xx xxxx
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