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

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

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

Abstract

AbstractThe 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 within vivomodels. Here, we utilize a relevant model of vascular-tissue interface with tunable endothelial permeabilityin vitrobased 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 vasculaturein 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.

Countries
United States, Singapore, Singapore
Keywords

capillary permeability, Cells, Science, 610, chemistry, 530, Models, Biological, Article, Capillary Permeability, Diffusion, Models, Lab-On-A-Chip Devices, Cyclic AMP, Human Umbilical Vein Endothelial Cells, Humans, cyclic AMP, human, procedures, Cells, Cultured, umbilical vein endothelial cell, cell culture, algorithm, Cultured, nanoparticle, diffusion, drug effect, Q, R, Dextrans, lab on a chip, biological model, Biological, nanomedicine, polystyrene derivative, Nanomedicine, dextran, Medicine, Nanoparticles, Polystyrenes, angiotensin I, Angiotensin I, metabolism, Algorithms

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
59
Top 10%
Top 10%
Top 10%
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gold