Scientific Reports (Mar 2017)

A Facile Method to Probe the Vascular Permeability of Nanoparticles in Nanomedicine Applications

  • Yan Teck Ho,
  • Giulia Adriani,
  • Sebastian Beyer,
  • Phan-Thien Nhan,
  • Roger D. Kamm,
  • James Chen Yong Kah

DOI
https://doi.org/10.1038/s41598-017-00750-3
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 13

Abstract

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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.