Nanoparticle Therapy for Vascular Diseases

Abstract

Nanoparticles promise to advance strategies to treat vascular disease. Since being harnessed by the cancer field to deliver safer and more effective chemotherapeutics, nanoparticles have been translated into applications for cardiovascular disease. Systemic exposure and drug-drug interactions remain a concern for nearly all cardiovascular therapies, including statins, antithrombotic, and thrombolytic agents. Moreover, off-target effects and poor bioavailability have limited the development of completely new approaches to treat vascular disease. Through the rational design of nanoparticles, nano-based delivery systems enable more efficient delivery of a drug to its therapeutic target or even directly to the diseased site, overcoming biological barriers and enhancing a drug's therapeutic index. In addition, advances in molecular imaging have led to the development of theranostic nanoparticles that may simultaneously act as carriers of both therapeutic and imaging payloads. The following is a summary of nanoparticle therapy for atherosclerosis, thrombosis, and restenosis and an overview of recent major advances in the targeted treatment of vascular disease.

Keywords: atherosclerosis; nanotechnology; restenosis; thrombosis; vascular diseases.

Figure 1:

Targeted therapeutic strategies enabled by nanoparticles. In order to avoid adverse effects and toxicities due to systemic exposure, targeted nanoparticles have been developed to resolve inflammation specifically at the inflamed plaque (e.g. Collagen-IV targeted IL-10 NPs), prevent plaque neovascularization (e.g. α_vβ₃-targed anti-angiogenic NPs), and deliver anti-proliferative or thrombolytic drugs to address restenosis and atherothrombotic events (e.g. endothelial-targeted NPs encapsulating paclitaxel, vWF-targeted NPs encapsulating tPA). Nanoparticles have also enabled cell-specific modulation of molecules that drive atherosclerosis, such as CD40-induced TRAF6 signaling in macrophages and regulation of PCSK9 in hepatocytes.

Figure 2:

Schematic of nanoparticles functionalized with agents that control their stability and interactions with the biological environment. A. Single-walled carbon nanotube (SWNT) tailored for vessel delivery of a therapeutic payload by coating the SWNT with polyethylene glycol (PEG) chains linked to arginine-glycine-aspartic acid (RGD), a potent α_vβ₃ integrin-binding peptide. B. Lipidoid nanoparticles that are formulated with phospholipids and cholesterol to facilitate intracellular delivery of siRNA for potent gene knockdown. Figures modified from [50] and [60].