Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis
Name
Kim-2014-Probing nanoparticle.pdf
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1.32 MB
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Checksum (MD5)
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Author(s)
Kim, YongTae
Lobatto, Mark E.
Kawahara, Tomohiro
Lee Chung, Bomy
Mieszawska, Aneta J.
Sanchez-Gaytan, Brenda L.
Fay, Francois
Senders, Max L.
Calcagno, Claudia
Becraft, Jacob Robert
Date Issued
January 2014
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Kim, Y., M. E. Lobatto, T. Kawahara, B. Lee Chung, A. J. Mieszawska, B. L. Sanchez-Gaytan, F. Fay, et al. “Probing Nanoparticle Translocation Across the Permeable Endothelium in Experimental Atherosclerosis.” Proceedings of the National Academy of Sciences 111, no. 3 (January 21, 2014): 1078–1083.
Version
Final published version
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1322725111
