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WIREs Nanomed Nanobiotechnol
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Optical molecular imaging of atherosclerosis using nanoparticles: shedding new light on the darkness

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Abstract The application of optical nanoparticles in cardiovascular research is increasing because of the high spatiotemporal resolution and high sensitivity of optical techniques as compared with other imaging platforms. The major cause of cardiovascular events is atherosclerosis, which is a chronic inflammation of the arterial wall. Interestingly, the composition rather than the size of nonstenotic atherosclerotic plaques and severe plaques with >90% stenosis are indicators for high‐risk vulnerability to rupture and acute cardiovascular events. Optical techniques may be highly suitable for discriminating, at subcellular resolution, the different stages of plaque progression by targeting bright and nontoxic optical nanoparticles toward distinct molecular epitopes in order to distinguish vulnerable from stable atherosclerotic plaques. Several optical techniques including two‐photon laser scanning microscopy (TPLSM), optical coherence tomography (OCT), and photoacoustic imaging (PAI) have been applied for (in vivo) characterization of atherosclerotic plaques, in addition to investigate their feasibility in the clinical setting. Optical nanoparticles, however, have predominantly been used in optical molecular imaging of tumors, but their application in cardiovascular research is increasing. In this review, we first describe shortly the basics of the mentioned optical techniques. Then, we detail on the most‐extensively studied optical nanoparticles and relatively new optical nanoparticles that hold promise for in vivo applications in atherosclerosis research. WIREs Nanomed Nanobiotechnol 2011 3 376–388 DOI: 10.1002/wnan.139 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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Schematic representation of the intrinsic properties of two‐photon laser scanning microscopy (TPLSM), optical coherence tomography (OCT), and photoacoustic imaging (PAI) regarding spatiotemporal resolution, sensitivity, and penetration depth. It should be noted that the sensitivity of TPLSM and PAI is in the pM and sub‐nM range, respectively, whereas the sensitivity of OCT is indicated by the minimally detectable reflection/scattering of the tissue, which is usually >100 dB, i.e., OCT is able to detect reflection/scattering of 10−10 of the incident optical power.

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Whole body near infrared region (NIR) fluorescence images of normal and tumor‐bearing mice after injection of the self‐quenched gold nanoparticle with and without a matrix metalloproteinases (MMP)‐2 inhibitor (a). NIR fluorescence images of excised tumors with and without MMP‐2 inhibitor (b). Immunohistology for tumors with and without MMP‐2 inhibitor (c). Quantitative analysis as function of time (circles: control mice; triangles: tumor‐bearing mice without MMP‐2 inhibitor; squares: tumor‐bearing mice with MMP‐2 inhibitor) (d). (Reprinted with permission from Ref 64. Copyright 2008 Wiley VCH)

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Transmission electron micrograph of Rhodamine B doped silica nanoparticles displaying uniform size distribution (left) and decreased photobleaching (right, brown dotted line) compared with Rhodamine B (right, orange dotted line) in solution. (Reprinted with permission from Ref 56. Copyright 2007 Elsevier)

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Ultrasound (a), photoacoustic (b), and combined (c) images of silver nanoparticles injected directly into an ex vivo canine pancreas. (Reprinted with permission from Ref 50. Copyright 2010 SPIE)

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Intravascular ultrasound (a), photoacoustic (b–d), and combined (e–g) images of the aorta from a diseased rabbit injected with macrophages loaded with gold nanoparticles. Photoacoustic images were obtained ex vivo at the wavelengths indicated, designating 700 nm as the wavelength at which the highest photoacoustic signal is obtained. (Reprinted with permission from Ref 47. Copyright 2009 American Chemical Society)

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Tumor targeting in living mice with RGD‐functionalized carbon nanotubes. Ultrasound image (gray) with photoacoustic overlay (green) at one transverse slice through the tumor (dotted black line). Mice injected with RGD‐functionalized carbon nanotubes showed an increased photoacoustic signal compared with mice injected with the RAD‐functionalized carbon nanotubes. (Reprinted with permission from Ref 26. Copyright 2010 American Chemical Society)

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Ex vivo macroscopic fluorescence imaging of en face aortas from wild‐type control mice and ApoE−/− mice (5 and 12 months old) injected with TCR+ and CD11b+ leukocytes, loaded with spectrally distinct quantum dots (QDs), i.e., QD585 (a) and QD655 (b). The leukocyte subsets colocalized with subsequent oil red O (ORO) staining (c). Fluorescence intensity, normalized to the wild‐type control group, increased with age (d). (Reprinted with permission from Ref 31. Copyright 2009 IOP Publishing Ltd)

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