Journal Article

Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis

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

2014

Overview

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.

• Publisher: National Academy of Sciences
• Subject: Albumins / Animals / Aorta / Atherosclerosis / Atherosclerosis - drug therapy / Atherosclerosis - physiopathology / Biological Sciences / Cancer / Design optimization / Disease Models, Animal / Drug Delivery Systems / endothelial cells / Endothelium / Endothelium - metabolism / Engineering / Gold - chemistry / Human Umbilical Vein Endothelial Cells / Humans / image analysis / Imaging / Magnetic Resonance Imaging / Male / Medical Sciences / Metal Nanoparticles - chemistry / Microcirculation / Microfluidics / Microscopy, Electron, Transmission / Microscopy, Fluorescence / Microvessels / Models, Theoretical / Nanomaterials / Nanomedicine / Nanoparticles / Nanotechnology / neoplasms / Permeability / Physical Sciences / Plaque, Atherosclerotic / Polymers / Rabbits / Shear Strength / Shear stress / Translocation