Nanoparticle uptake by macrophages in vulnerable plaques for atherosclerosis diagnosis (original) (raw)
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Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2011
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.
Intravascular Imaging of Atherosclerosis by Using Engineered Nanoparticles
Biosensors
Atherosclerosis is a leading cause of morbidity and mortality, and high-risk atherosclerotic plaques can result in myocardial infarction, stroke, and/or sudden death. Various imaging and sensing techniques (e.g., ultrasound, optical coherence tomography, fluorescence, photoacoustic) have been developed for scanning inside blood vessels to provide accurate detection of high-risk atherosclerotic plaques. Nanoparticles have been utilized in intravascular imaging to enable targeted detection of high-risk plaques, to enhance image contrast, and in some applications to also provide therapeutic functions of atherosclerosis. In this paper, we review the recent progress on developing nanoparticles for intravascular imaging of atherosclerosis. We discuss the basic nanoparticle design principles, imaging modalities and instrumentations, and common targets for atherosclerosis. The review is concluded and highlighted with discussions on challenges and opportunities for bringing nanoparticles int...
Molecular imaging, 2015
AbstractRecently, an apolipoprotein E-deficient (ApoE-/-) mouse model with a mutation (C1039G+/-) in the fibrillin-1 (Fbn1) gene (ApoE-/-Fbn1C1039G+/- mouse model) was developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE-/- mouse model, where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aimed to measure and quantify in vivo the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold nanoparticle-enhanced micro-computed tomography (microCT) scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the microCT scans, regions of the artery wall with contrast agent present were calculated and visualized in three dimensions. From this information, the contrast-enhanced area and contrast-enhanced centerline length were calculate...
Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis
CIRCULATION, 2008
Background-Macrophages participate centrally in atherosclerosis, and macrophage markers (eg, CD68, correlate well with lesion severity and therapeutic modulation. On the basis of the avidity of lesional macrophages for polysaccharide-containing supramolecular structures such as nanoparticles, we have developed a new positron emission tomography (PET) agent with optimized pharmacokinetics to allow in vivo imaging at tracer concentrations. Methods and Results-A dextranated and DTPA-modified magnetofluorescent 20-nm nanoparticle was labeled with the PET tracer 64 Cu (1 mCi/0.1 mg nanoparticles) to yield a PET, magnetic resonance, and optically detectable imaging agent. Peak PET activity 24 hours after intravenous injection into mice deficient in apolipoprotein E with experimental atherosclerosis mapped to areas of high plaque load identified by computed tomography such as the aortic root and arch and correlated with magnetic resonance and optical imaging. Accumulated dose in apolipoprotein E-deficient aortas determined by gamma counting was 260% and in carotids 392% of respective wild-type organs (PϽ0.05 both). Autoradiography of aortas demonstrated uptake of the agent into macrophage-rich atheromata identified by Oil Red O staining of lipid deposits. The novel nanoagent accumulated predominantly in macrophages as determined by fluorescence microscopy and flow cytometry of cells dissociated from aortas. Conclusions-This report establishes the capability of a novel trimodality nanoparticle to directly detect macrophages in atherosclerotic plaques. Advantages include improved sensitivity; direct correlation of PET signal with an established biomarker (CD68); ability to readily quantify the PET signal, perform whole-body vascular surveys, and spatially localize and follow the trireporter by microscopy; and clinical translatability of the agent given similarities to magnetic resonance imaging probes in clinical trials. (Circulation. 2008;117:379-387.)
ACS omega, 2018
In this work, we present a novel, simple, and highly accurate three-dimensional (3D) diffusion reflection (DR) imaging system and method for the detection of accumulation sites of gold nanorods (GNRs) within the tissue. GNRs are intensively used for diagnosis purposes of varied diseases, mainly because of their ability to well absorb visible light, which introduces them as terrific contrast agents in various imaging and theranostics methods. Lately, these GNRs unique absorption properties have served in DR intensitybased measurements, suggesting a novel diagnostic tool, DR-GNRs. In this paper, we show a new measurement system and method for DR, based on its radial collection from the tissue. These radial measurements enabled a unique 3D presentation of the DR-GNR, introducing the dimensions ρ for the radius, θ for the angle, and Γ for the reflected intensity. On the basis of the diffusion model, which enables to correlate between the sample's optical properties and its reflectance, a unique, radial map is presented. This map introduces the slopes of the DR curves in each measured angle, which are linearly correlated with the tissue's optical properties and with the GNRs concentrations within the tissue, thus enables the exact radial localization of the GNRs in the sample. We show the detection of macrophage accumulation in tissue-like phantoms, as well as the localization of unstable plaques in hyperlipidemic mice, in vivo. This highly accurate, powerful technology paves the way toward a real-time detection method that can be successfully integrated in the rapid increasing field of personalized medicine.
Nano Letters, 2014
In this study we report the use of gold nanorods (GNRs) as absorption contrast agents in the diffusion reflection (DR) method for the in vivo detection of atherosclerotic injury. The early detection and characterization of atherosclerotic vascular disease is considered to be one of the greatest medical challenges today. We show that macrophage cells, which are major components of unstable active atherosclerotic plaques, uptake gold nanoparticles, resulting in a change in the optical properties of tissue-like phantoms and a unique DR profile. In vivo DR measurements of rats that underwent injury of the carotid artery showed a clear difference between the DR profiles of the injured compared with healthy arteries. The results suggest that DR measurements following GNRs administration represent a potential novel method for the early detection of atherosclerotic vascular disease.
Journal of Biophotonics, 2018
Atherosclerosis (AS), the leading cause of morbidity and mortality in cardiovascular disease, needs an early detection for treatment and prevention of fatal events. Here, for the first time, we applied gold nanorods (GNRs)‐assisted diffusion reflection (DR), a noninvasive technique for in vivo detection of AS in a high‐fat‐diet‐induced c57bl mouse model, which resembles the manifestation of AS in humans. DR simply detects the change in light reflection profile of tissue due to the accumulation of GNRs in the AS plaques and enables clear detection of AS lesions in carotid and femoral arteries of these hyperlipidemic mice. After 24 hours post‐GNRs injection, DR showed the highest efficiency of AS detection. Moreover, the sensitivity of the DR method is much higher than computed tomography (CT) and is comparable to ex vivo high‐resolution CT. Our results strongly suggest that the DR method can detect early atherosclerotic lesions in a sensitive and specific manner.
Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography
Nature Medicine, 2007
Sudden fibrous cap disruption of 'high-risk' atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary arteries, causing acute coronary syndromes. High-risk atherosclerotic plaques are characterized by their specific cellular and biological content (in particular, a high density of macrophages), rather than by their impact on the vessel lumen. Early identification of high-risk plaques may be useful for preventing ischemic events. One major hurdle in detecting high-risk atherosclerotic plaques in coronary arteries is the lack of an imaging modality that allows for the identification of atherosclerotic plaque composition with high spatial and temporal resolutions. Here we show that macrophages in atherosclerotic plaques of rabbits can be detected with a clinical X-ray computed tomography (CT) scanner after the intravenous injection of a contrast agent formed of iodinated nanoparticles dispersed with surfactant. This contrast agent may become an important adjunct to the clinical evaluation of coronary arteries with CT.