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WIREs Nanomed Nanobiotechnol
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Nanoparticles as magnetic resonance imaging contrast agents for vascular and cardiac diseases

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Abstract Advances in nanoparticle contrast agents for molecular imaging have made magnetic resonance imaging a promising modality for noninvasive visualization and assessment of vascular and cardiac disease processes. This review provides a description of the various nanoparticles exploited for imaging cardiovascular targets. Nanoparticle probes detecting inflammation, apoptosis, extracellular matrix, and angiogenesis may provide tools for assessing the risk of progressive vascular dysfunction and heart failure. The utility of nanoparticles as multimodal probes and/or theranostic agents has also been investigated. Although clinical application of these nanoparticles is largely unexplored, the potential for enhancing disease diagnosis and treatment is considerable. WIREs Nanomed Nanobiotechnol 2011 3 146–161 DOI: 10.1002/wnan.114 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease

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Schematic structures for several nanoparticles: iron oxide with surface coating, micelle, micelle with core of nanoparticles, liposome, discoidal high‐density lipoprotein (HDL), spherical HDL, and oil‐in‐water emulsion. (Targeting molecules: ligands, peptides, and antibodies; apoAI: apolipoprotein A I; CE: cholesteryl ester; TG: triglyceride).

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Typical short‐axis magnetic resonance (MR) images with an echo time (TE) of (a) 2.9 ms and (b) 6.0 ms for a myocardial infarction (MI) mouse injected with cNGR‐pQDs (left), an MI mouse injected with unlabeled QDs (middle), and a sham‐operated mouse injected with cNGR‐pQDs (right). Arrowheads indicate the hypointense area for MI mouse injected with cNGR‐pQDs. (c) Two‐photon laser‐scanning microscopy revealed that cNGR‐pQDs were mainly in the (2) border zone and (3) infarct areas, but not in (1) remote myocardium. Arrows indicate the colocalization of nanoparticles with vasculature. Red: quantum dots; Green: α‐CD31‐FITC. (Reprinted with permission from Ref 102. Copyright 2010 American Heart Association, Inc.).

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Typical T1‐weighted magnetic resonance (MR) images of the apoE−/− mouse aorta (a, b) pre‐ and (d, e) 24 h postinjection with either Au‐HDL or QD‐HDL. Arrows point to areas enhanced in the post images. T2*‐weighted images of an apoE−/− mouse aorta (c) pre‐ and (f) 24 h postinjection with FeO‐HDL. (g, h, i) Confocal microscopy images of the apoE−/− mouse aortic sections. Red: nanocrystal HDL; Green: macrophages; Blue: nuclei. The arrowheads indicate colocalization of nanocrystal HDL with macrophages. (Reprinted with permission from Ref 54. Copyright 2008 American Chemical Society).

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Schematic illustration (left) and TEM image (middle) of colloidal iron oxide nanoparticles (CIONs), and a T1‐weighted magnetic resonance (MR) image of a human carotid endarterectomy specimen (right). (Reprinted with permission from Ref 53. Copyright 2009 American Chemical Society).

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Typical in vivo 19F magnetic resonance (MR) images of myocardial infarction after injection of perfluorocarbon emulsions. (a) 1H and 19F MR images at the same position of a mouse thorax recorded 4 days after ligation of the left anterior descending artery. 19F signal is near the infarcted region (I) and at the location of surgery (T). (b) Sections of 1H images superimposed with 19F images (red) at same position acquired 1, 3, and 6 days after surgery. (Reprinted with permission from Ref 86. Copyright 2008 American Heart Association, Inc.).

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Typical gradient echo (GRE) and GRE acquisition for superparamagnetic particles (GRASP) images of the rabbit aorta (red arrow) pre‐ and 24 h postinjection of fractionated Feridex or Feridex at 4.8 mg Fe/kg of bodyweight. (Reprinted with permission from Ref 42. Copyright 2008 John Wiley and Sons, Ltd).

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(a) Cryo‐TEM image of bare liposomes. (b) 3D reconstruction of CNA35‐functionalized liposomes from a series of TEM images. Red: lipid bilayer; Blue: individual CNA35 proteins. (c) T1‐map of bovine collagen type I matrices treated with (1) buffer, (2) bare liposomes and (3) CNA35‐functionalized liposomes. (d) Surface relaxation rate of bovine collagen type I showed a linear correlation with the molar fraction of Gd‐DTPA‐BSA in the CNA35‐functionalized liposomes. (Reprinted with permission from Ref 72. Copyright 2009 John Wiley and Sons, Ltd).

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Typical in vivo magnetic resonance (MR) images pre‐ and postinjection of macrophage‐targeted immunomicelles (a and b), untargeted micelles (c), and Gd‐DTPA (d) in apoE−/− mice (insets are enlargements of the aortas). The right side of (a)–(d) shows H&E staining of the aorta at the identical anatomic level as the MR images from the same animal. (Reprinted with permission from Ref 9. Copyright 2007 National Academy of Sciences, USA).

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Representative in vivo magnetic resonance (MR) images of apoE−/− heart (a) pre‐ and (b) 48 h postinjection of VCAM‐1 targeting iron oxide nanoparticles (VINP‐28). Dotted line shows the location of short‐axis view for the insets (lower panel with color‐coded signal intensity). (c) The location of VINP‐28 under fluorescent microscopy was associated with (d) VCAM‐1 expression in immunohistochemistry. (Reprinted with permission from Ref 48. Copyright 2006 American Heart Association, Inc.).

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Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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