A Facile Method to Probe the Vascular Permeability of Nanoparticles in Nanomedicine Applications
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Ho-2017-A Facile Method to Probe the Vascular.pdf
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Author(s) • • • • •
Ho, Yan Teck
Adriani, Giulia
Beyer, Sebastian
Nhan, Phan-Thien
Kah, James Chen Yong
Kamm, Roger Dale
Date Issued
March 2017
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Ho, Yan Teck; Adriani, Giulia; Beyer, Sebastian; Nhan, Phan-Thien; Kamm, Roger D. and Kah, James Chen Yong. “A Facile Method to Probe the Vascular Permeability of Nanoparticles in Nanomedicine Applications.” Scientific Reports 7, no. 1 (March 2017): 707 © 2017 The Author(s)
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Final published version
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 Pd of 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 Pd that approximated tumor vasculature while HUVECs treated with 25 μg/mL cAMP had Pd that approximated healthy vasculature in vivo. As the size of pNPs increased, its Pd decreased 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
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DOI of Published Version
https://doi.org/10.1038/s41598-017-00750-3