Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis

• Published in: Proceedings of the National Academy of Sciences - PNAS 2014-01, Vol.111 (3), p.1078-1083
• Main Authors: Kim, YongTae, Lobatto, Mark E., Kawahara, Tomohiro, Chung, Bomy Lee, Mieszawska, Aneta J., Sanchez-Gaytan, Brenda L., Fay, Francois, Senders, Max L., Calcagno, Claudia, Becraft, Jacob, Saung, May Tun, Gordon, Ronald E., Stroes, Erik S. G., Ma, Mingming, Farokhzad, Omid C., Fayad, Zahi A., Mulder, Willem J. M., Langer, Robert
• Format: Article
• Language: English
• Subjects: Albumins; Animals; Aorta; Atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - physiopathology; Biological Sciences; Cancer; Design optimization; Disease Models, Animal; Drug Delivery Systems; Endothelium; Endothelium - metabolism; Gold - chemistry; Human Umbilical Vein Endothelial Cells; Humans; Imaging; Magnetic Resonance Imaging; Male; Metal Nanoparticles - chemistry; Microcirculation; Microfluidics; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Microvessels; Models, Theoretical; Nanomaterials; Nanomedicine; Nanoparticles; Nanotechnology; Permeability; Physical Sciences; Plaque, Atherosclerotic; Rabbits; Shear Strength; Shear stress
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1322725111

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.