Macrophage-targeted nanomedicine for the diagnosis and treatment of atherosclerosis

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.

Abstract

In this Review, Tao and colleagues discuss the latest advances in nanoparticle-based imaging and therapeutic approaches targeting macrophages in atherosclerotic plaques, highlight opportunities for novel macrophage-targeting nanomedicines for atherosclerosis diagnosis and treatment, and provide solutions to challenges in this area to accelerate clinical translation.

Key points

• Because macrophages have key roles in atherosclerosis progression, macrophage-mediated pro-atherosclerotic processes are important targets for both diagnostic imaging and novel therapies for atherosclerosis.

• Nanotechnology is particularly advantageous in its capacity to substantially improve the pharmacokinetic profile and chemical stability of encapsulated diagnostic and therapeutic agents for atherosclerosis management.

• The rational design of nanoparticle-based imaging agents that can specifically target inflammatory macrophages in atherosclerotic plaques offers diagnostic potential to non-invasively quantify atherosclerosis plaque burden, evaluate the efficacy of medical interventions and serve as surrogate end points.

• 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.

• Rapid advances in nanotechnology and bioengineering and an improved understanding of atherosclerotic pathophysiology have accelerated the development of novel nanotherapeutics for atherosclerosis diagnosis and treatment.

• The success of various nanomedicine-based approaches in preclinical studies of atherosclerosis and their use in human cancer bode well for their future application in the diagnosis and treatment of patients with cardiovascular disease.