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      Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis.

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          Abstract

          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.

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          Author and article information

          Journal
          Proc. Natl. Acad. Sci. U.S.A.
          Proceedings of the National Academy of Sciences of the United States of America
          1091-6490
          0027-8424
          Jan 21 2014
          : 111
          : 3
          Affiliations
          [1 ] The 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.
          Article
          1322725111
          10.1073/pnas.1322725111
          24395808
          ee03614e-f9b5-413f-8863-65c3f76996af
          History

          cardiovascular disease,microfluidics,nanotechnology,noninvasive imaging

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