title: Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis.
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.
authors.affiliation: The George W. Woodruff School of Mechanical Engineering, Institute for Electronics and Nanotechnology, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Yongtae
authors.initials: Y
authors.lastname: Kim
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lobatto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kawahara
authors.forename: Bomy
authors.initials: B
authors.lastname: Lee Chung
authors.forename: Aneta J
authors.initials: AJ
authors.lastname: Mieszawska
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Sanchez-Gaytan
authors.forename: Francois
authors.initials: F
authors.lastname: Fay
authors.forename: Max L
authors.initials: ML
authors.lastname: Senders
authors.forename: Claudia
authors.initials: C
authors.lastname: Calcagno
authors.forename: Jacob
authors.initials: J
authors.lastname: Becraft
authors.forename: May
authors.initials: M
authors.lastname: Tun Saung
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gordon
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
authors.forename: Mingming
authors.initials: M
authors.lastname: Ma
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004727:Endothelium / Q000378:metabolism*; D006046:Gold / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D008833:Microcirculation; D044085:Microfluidics; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008962:Models, Theoretical; D010539:Permeability; D058226:Plaque, Atherosclerotic; D011817:Rabbits; D033081:Shear Strength
chemical_list: D006046:Gold
keywords: cardiovascular disease; microfluidics; nanotechnology; noninvasive imaging