A Facile Method to Probe the Vascular Permeability of Nanoparticles in Nanomedicine Applications
A Facile Method to Probe the Vascular Permeability of Nanoparticles in Nanomedicine Applications
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.
- Federal Institute For Materials Research and Testing Germany
- National University of Singapore Libraries Singapore
- National University of Singapore Singapore
- Singapore-MIT Alliance for Research and Technology Singapore
- Massachusetts Institute of Technology United States
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
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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