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WIREs Nanomed Nanobiotechnol
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Development and application of endothelium‐targeted microparticles for molecular magnetic resonance imaging

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Abstract Molecular imaging of disease states can enhance diagnosis allowing for accurate and more effective treatment. By specifically targeting molecules differentially expressed in disease states, researchers and clinicians have a means of disease characterization at a cellular or tissue level. Targeted micron‐sized particles of iron oxide (MPIO) have been used as molecule‐specific contrast agents for use with magnetic resonance imaging (MRI), and early evidence suggests they may be suitable for use with other imaging modalities. Targeting of MPIO to markers of disease is commonly achieved through the covalent attachment of antibodies to the surface of the particles, providing an imaging agent that is both highly specific and which binds with high affinity. When comparing micron‐sized particles with nanometre‐sized particles, the former provide substantial signal dropout in MRI and confer the sensitivity to detect low levels of target. Furthermore, larger particles appear to bind to targets more potently than smaller particles. Animal models have also demonstrated favorable blood clearance characteristics of MPIO, which are important in achieving favorable signal over background and to attain clearance and disposal. Although the current generation of commercially available MPIO are not suitable for administration into humans, future work may focus on the development of biodegradable and nonimmunogenic MPIO that may allow the use of these imaging agents in a clinical setting. WIREs Nanomed Nanobiotechnol 2012, 4:247–256. doi: 10.1002/wnan.1164 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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Brightfield microscopy of micron‐sized particles of iron oxide (MPIO) bound to endothelial cells in vitro. One micron MPIO targeted to platelet endothelial cell adhesion molecule (PECAM)‐1 on cultured human umbilical vein endothelial cells (HUVEC) and imaged using phase contrast (a); 4.5 µm MPIO bound to PECAM‐1 on HUVEC and imaged using differential phase interference (DIC) microscopy (b).

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Micron‐sized particles of iron oxide (MPIO) in clinical imaging modalities. In vivo administration of 4.5 µm MPIO with subsequent ex vivo magnetic resonance imaging (MRI) showing detection of particles (arrow) bound to P‐selectin and vascular cell adhesion molecule (VCAM)‐1 in the aortic root following injection (a). Optical coherence tomography (OCT) image demonstrating the scattering effect of MPIO bound to platelet endothelial cell adhesion molecule (PECAM)‐1 on a monolayer of cultured human umbilical vein endothelial cells (HUVEC) (b). In vivo MRI of 1 µm MPIO bound to P‐selectin and VCAM‐1 in the aortic root of a 20‐week old chow‐fed ApoE−/− mouse, 60 min post‐injection (c).

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Fluorescence microscopy and histology of targeted micron‐sized particles of iron oxide (MPIO). 1 µm MPIO targeted to vascular cell adhesion molecule (VCAM)‐1 (green) were labeled with Alexa Fluor 488 and incubated with cells that had been stained for VCAM‐1 and detected using Alexa Fluor 594 (red), showing colocalization of MPIO with protein (a). 1 µm MPIO targeted to platelet endothelial cell adhesion molecule (PECAM)‐1 (green) colocalize with antibody staining for PECAM‐1 (red) (b). Histology section showing binding of 4.5 µm MPIO targeted to both P‐selectin and VCAM‐1 in the aortic root following injection of MPIO (c).

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Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease
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