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

作者：Ho Yan Teck; Adriani Giulia; Beyer Sebastian; Phan Thien Nhan; Kamm Roger D; Kah James Chen Yong

来源：Scientific Reports, 2017, 7(1): 707.

DOI：10.1038/s41598-017-00750-3

<jats:title>Abstract</jats:title><jats:p>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 (P<jats:sub>d</jats:sub>) of NPs is difficult with <jats:italic>in vivo</jats:italic> models. Here, we utilize a relevant model of vascular-tissue interface with tunable endothelial permeability <jats:italic>in vitro</jats:italic> 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 P<jats:sub>d</jats:sub> 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 P<jats:sub>d</jats:sub> that approximated tumor vasculature while HUVECs treated with 25 μg/mL cAMP had P<jats:sub>d</jats:sub> that approximated healthy vasculature <jats:italic>in vivo</jats:italic>. As the size of pNPs increased, its P<jats:sub>d</jats:sub> 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.</jats:p>

• 出版日期2017-3-31