Emerging applications of nanotechnology for the diagnosis and management of vulnerable atherosclerotic plaques

Abstract

An estimated 16 million people in the United States have coronary artery disease (CAD), and approximately 325,000 people die annually from cardiac arrest. About two-thirds of unexpected cardiac deaths occur without prior recognition of cardiac disease. A vast majority of these deaths are attributable to the rupture of ‘Vulnerable atherosclerotic plaques’. Clinically, plaque vulnerability is typically assessed through imaging techniques, and ruptured plaques leading to acute myocardial infarction are treated through angioplasty or stenting. Despite significant advances, it is clear that current imaging methods are insufficiently capable for elucidating plaque composition—which is a key determinant of vulnerability. Further, the exciting improvement in the treatment of CAD afforded by stenting procedures has been buffered by significant undesirable host-implant effects, including restenosis and late thrombosis. Nanotechnology has led to some potential solutions to these problems by yielding constructs that interface with plaque cellular components at an unprecedented size scale. By leveraging the innate ability of macrophages to phagocytose nanoparticles, contrast agents can now be targeted to plaque inflammatory activity. Improvements in nano-patterning procedures have now led to increased ability to regenerate tissue isotropy directly on stents, enabling gradual regeneration of normal, physiologic vascular structures. Advancements in immunoassay technologies promise lower costs for biomarker measurements, and in the near future, may enable the addition of routine blood testing to the clinician’s toolbox—decreasing the costs of atherosclerosis-related medical care. These are merely three examples among many stories of how nanotechnology continues to promise advances in the diagnosis and treatment of vulnerable atherosclerotic plaques.

Development of a Magnetic Resonance Imaging Protocol for the Characterization of Atherosclerotic Plaque by Using Vascular Cell Adhesion Molecule-1 and Apoptosis-Targeted Ultrasmall Superparamagnetic Iron Oxide Derivatives

“…[41][42][43][44][45][46][47][48][49] Nevertheless, these functionalized nanoparticles present several drawbacks that limit their perspectives for clinical applications.…”

Macrophage-Specific RNA Interference Targeting via “Click”, Mannosylated Polymeric Micelles

“…19, 38 Nanoparticle-mediated drug delivery is an attractive way to achieve this goal, because macrophages are phagocytes capable of efficiently internalizing particulate substances. 39, 40 However, macrophages play functional roles in maintaining healthy physiology of many tissues, including bone, liver, and spleen.…”

“…Alternative strategies require expensive technologies with uncertain practical clinical applicability, such as macrophage extraction, ex vivo modification, and adoptive transfer; 8 antibody-nanoparticle conjugates; 16, 17 or custom phospholipids, 18 as reviewed elsewhere. 19 Very few of these proposed approaches can be practically scaled for pharmaceutical purposes. Some of these methods deliver drugs to multiple cell types non-specifically, and systemic interference with macrophage behavior may lead to unintended side effects, including autoimmune manifestations.…”

Evolution and rupture of vulnerable plaques: a review of mechanical effects

“…In in vitro imaging techniques, spatial resolution up to 23 µm can be obtained with MRI, 69,70 and up to 1.7 µm with microcomputed tomography (recent results obtained by our group at the Swiss Light Source, Figure 4). In addition to these approaches, new techniques are emerging, such as nanoparticle technologies 71,72 coupled to traditional imaging methods (eg, MRI). By this technology, the core of the plaque can be tracked using specific nanoparticles embedded in a convenient product that targets the cells needed to be observed.…”