title: A Facile Method to Probe the Vascular Permeability of Nanoparticles in Nanomedicine Applications.
abstract: The effectiveness of nanoparticles (NP) in nanomedicine depends on their ability to extravasate from vasculature towards the target tissue. This is determined by their permeability across the endothelial barrier. Unfortunately, a quantitative study of the diffusion permeability coefficients (Pd) of NPs is difficult with in vivo models. Here, we utilize a relevant model of vascular-tissue interface with tunable endothelial permeability in vitro based on microfluidics. Human umbilical vein endothelial cells (HUVECs) grown in microfluidic devices were treated with Angiopoietin 1 and cyclic adenosine monophosphate (cAMP) to vary the Pdof the HUVECs monolayer towards fluorescent polystyrene NPs (pNPs) of different sizes, which was determined from image analysis of their fluorescence intensity when diffusing across the monolayer. Using 70 kDa dextran as a probe, untreated HUVECs yielded a Pdthat approximated tumor vasculature while HUVECs treated with 25 μg/mL cAMP had Pdthat approximated healthy vasculature in vivo. As the size of pNPs increased, its Pddecreased in tumor vasculature, but remained largely unchanged in healthy vasculature, demonstrating a trend similar to tumor selectivity for smaller NPs. This microfluidic model of vascular-tissue interface can be used in any laboratory to perform quantitative assessment of the tumor selectivity of nanomedicine-based systems.
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Yan Teck
authors.initials: YT
authors.lastname: Ho
authors.affiliation: BioSyM Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore.
authors.forename: Giulia
authors.identifier: http://orcid.org/0000-0002-7505-1668
authors.initials: G
authors.lastname: Adriani
authors.affiliation: BioSyM Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore.|Federal Institute for Materials Research and Testing, Germany, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Beyer
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore.|Department of Mechanical Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Phan-Thien
authors.initials: PT
authors.lastname: Nhan
authors.affiliation: BioSyM Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore. rdkamm@mit.edu.|Department of Biological Engineering and Department of Mechanical Engineering, Massachusetts Institute of Technology, Massachusetts, USA. rdkamm@mit.edu.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kamm
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore. biekahj@nus.edu.sg.|Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore. biekahj@nus.edu.sg.
authors.forename: James Chen Yong
authors.identifier: http://orcid.org/0000-0002-2247-6929
authors.initials: JCY
authors.lastname: Kah
mesh_terms: D000465:Algorithms; D000803:Angiotensin I / Q000378:metabolism / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D003911:Dextrans / Q000378:metabolism; D004058:Diffusion; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008954:Models, Biological; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry
chemical_list: D003911:Dextrans; D011137:Polystyrenes; D000803:Angiotensin I; D000242:Cyclic AMP