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Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1078-83. doi: 10.1073/pnas.1322725111. Epub 2014 Jan 6.

Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis.

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  • 1The George W. Woodruff School of Mechanical Engineering, Institute for Electronics and Nanotechnology, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332.


Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid-polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system.


cardiovascular disease; microfluidics; nanotechnology; noninvasive imaging

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