Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis

Yongtae Kim, Mark E. Lobatto, Tomohiro Kawahara, Bomy Lee Chung, Aneta J. Mieszawska, Brenda L. Sanchez-Gaytan, Francois Fay, Max L. Senders, Claudia Calcagno, Jacob Becraft, May Tun Saung, Ronald E. Gordon, Erik S.G. Stroes, Mingming Ma, Omid C. Farokhzad, Zahi A. Fayad, Willem J.M. Mulder, Robert Langer

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1078-1083
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number3
DOIs
StatePublished - Jan 21 2014

    Fingerprint

Keywords

  • Cardiovascular disease
  • Microfluidics
  • Nanotechnology
  • Noninvasive imaging

ASJC Scopus subject areas

  • General

Cite this

Kim, Y., Lobatto, M. E., Kawahara, T., Chung, B. L., Mieszawska, A. J., Sanchez-Gaytan, B. L., Fay, F., Senders, M. L., Calcagno, C., Becraft, J., Saung, M. T., Gordon, R. E., Stroes, E. S. G., Ma, M., Farokhzad, O. C., Fayad, Z. A., Mulder, W. J. M., & Langer, R. (2014). Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis. Proceedings of the National Academy of Sciences of the United States of America, 111(3), 1078-1083. https://doi.org/10.1073/pnas.1322725111