Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 3, Pages 1078-1083Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1322725111
Keywords
nanotechnology; cardiovascular disease; microfluidics; noninvasive imaging
Categories
Funding
- National Institutes of Health (NIH)-National Cancer Institute shared resources [R24 CA095823-04]
- National Science Foundation Major Research Instrumentation [DBI-9724504]
- NIH shared instrumentation [1 S10 RR0 9145-01]
- National Heart, Lung, and Blood Institute
- NIH [HHSN268201000045C, R01 EB009638, R01CA155432]
- National Cancer Institute [CA151884]
- David H. Koch Prostate Cancer Foundation Award in Nanotherapeutics
- European Framework Program 7
- Netherlands Organization for Scientific Research ZonMW Vidi [91713324]
- Dutch Network for Nanotechnology NanoNext NL
- International Atherosclerosis Society and the Foundation De Drie Lichten in the Netherlands
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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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