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WIREs Nanomed Nanobiotechnol
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Multifunctional imaging nanoprobes

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Abstract Multifunctional imaging nanoprobes have proven to be of great value in the research of pathological processes, as well as the assessment of the delivery, fate, and therapeutic potential of encapsulated drugs. Moreover, such probes may potentially support therapy schemes by the exploitation of their own physical properties, e.g., through thermal ablation. This review will present four classes of nanoparticulate imaging probes used in this area: multifunctional probes (1) that can be tracked with at least three different and complementary imaging techniques, (2) that carry a drug and have bimodal imaging properties, (3) that are employed for nucleic acid delivery and imaging, and (4) imaging probes with capabilities that can be used for thermal ablation. We will highlight several examples where the suitable combination of different (bio)materials like polymers, inorganic nanocrystals, fluorophores, proteins/peptides, and lipids can be tailored to manufacture multifunctional probes to accomplish nanomaterials of each of the aforementioned classes. Moreover, it will be demonstrated how multimodality imaging approaches improve our understanding of in vivo nanoparticle behavior and efficacy at different levels, ranging from the subcellular level to the whole body. WIREs Nanomed Nanobiotechnol 2010 2 138–150 This article is categorized under: Diagnostic Tools > Biosensing

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A generalized schematic of the ways in which a nanoparticle may be targeted, made biocompatible, and carry payloads such as drugs or contrast inducing materials.

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(a) Schematic depiction of an iron oxide based MR contrast agent that can deliver siRNA. (b) MR image of a mouse pre‐ and 24 h postadministration of the agent. Change in pixel color in the tumor (arrow) from reddish yellow to blue indicates accumulation of the agent. (c) Fluorescence image of the mouse with emission seen from the tumor, also indicating agent accumulation. (d) Silencing of the Birc5 gene by the siRNA reduces Survivin expression in the tumor and leads to apoptosis in this tissue. Reproduced with permission from the publisher.57.

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(a) Synthetic procedure used to prepare micellar hybrid nanoparticles that encapsulate magnetic nanoparticles and quantum dots within a single PEG‐modified phopholipid micelle. (b) Multimodal images (NIR fluorescence in the Cy5.5 channel and MRI) of PBS and MDA‐MB‐435 human carcinoma cells that were left untreated, were treated with untargeted nanoparticles and with targeted nanoparticles. (c) Targeted drug delivery of nanoparticles containing DOX into MDAMB‐435 human carcinoma cells. The DOX‐loaded nanoparticles were incubated with the cells for 2 h. Arrowheads indicate colocalization of DOX and nanoparticles. The inset shows the colocalization of some DOX (red) and the endosome marker (green) 30 min after incubation with DOX‐loaded nanoparticles. The nuclei were stained with 4‐6‐diamidino‐2‐phenylindole. Reproduced with permission from the publisher.54.

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Histological examination of α5β1‐integrin expression and nanoparticle localization. (a) Fluorescent microscopy images (×200) of conventional immunohistochemistry of 8 µm sections of tumor border stained for α5β1‐integrin (green) and endothelium (red), with nuclei counterstained blue. There is prevalent expression of α5β1‐integrin throughout the tissue section, both within and outside of the vasculature. (b) The merged images confirm that the nanoparticles colocalized with the angiogenic vasculature, and did not reach the α5β1‐integrin expressed by tumor and other cells in the extravascular matrix. Reproduced with permission from the publisher.51.

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(a) Schematic depiction of gold core high density lipoprotein (Au‐HDL). The particle corona consists of ordinary phospolipids, paramagnetic lipids, fluorescent lipids and apolipoprotein A‐I. T1‐weighted MR images of the aorta of an apoE‐KO mouse (b) before and (c) 24 h postinjection with Au‐HDL. (d) Confocal microscopy image of an aortic section revealed colocalization of nanocrystal HDL (red) with macrophages (green) as indicated by arrowheads. The nuclei are depicted in blue. (e) Ex vivo sagittal CT image of an aorta of a mouse injected with Au‐HDL. (f) Corresponding fluorescence image of the aorta depicted in (e). Reproduced with permission from the publisher.48.

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Top: Schematic depiction of quantum dot containing silica particle with a lipid coating. (a) Determination of blood circulation half‐life values by fluorescence imaging (left) and magnetic resonance angiography (right). (b) Confocal microscopy of sections from different organs collected from mice at 24 h after injection and stained for endothelial cells to visualize blood vessels (green) and nuclei (blue), shows particle accumulation in red. (c) TEM was used to show particle uptake by cells in the liver, spleen, and lung. Reproduced with permission from the publisher.44.

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Paramagnetic QD‐micelles for multimodality imaging. (a) Schematic depiction of αvβ3‐specific and paramagnetic QD‐micelles. (b) Intravital microscopy brightfield (left) and fluorescence (right) images of microvessels in tumor‐bearing mice after intravenous injection of RGD‐pQDs. (c) Fluorescence image of a tumor‐bearing mouse following intravenous administration of the nanoparticle agent. (d) T1‐weighted MR images before and 45 min after the injection of the αvβ3‐specific and paramagnetic QD‐micelles. Reproduced with permission from the publisher.36,37.

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(a) Schematic of the trimodality reporter 64Cu‐TNP. The chelator DTPA allows attachment of radiotracer 64Cu, the iron oxide core provides contrast in MRI and the fluorophore for fluorescence techniques. (b), (c) 64Cu‐TNP accumulates in atherosclerotic lesions; PET‐CT shows enhancement of the posterior aortic root (arrow). (d) Preinjection and (e) postinjection MRIs of the aortic root (inset). The dotted line in the long‐axis views demonstrates slice orientation for shortaxis root imaging. Signal intensity (pseudocolored with identical scaling for preinjection and postinjection image) decreased significantly after injection of 64Cu‐TNP. (f) Near‐infrared fluorescence reflectance imaging (NIRF) of excised aortas shows accumulation of the probe in plaques residing in the root, thoracic aorta, and carotid bifurcation. Reproduced with permission from the publisher.42.

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