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Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow
Vascular endothelium is a potential target for therapeutic intervention in diverse pathological processes, including inflammation, atherosclerosis, and thrombosis. By virtue of their intravascular topography, endothelial cells are exposed to dynamically changing mechanical forces that are generated...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384367/ https://www.ncbi.nlm.nih.gov/pubmed/22745555 http://dx.doi.org/10.2147/IJN.S30624 |
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author | Samuel, Stephen Paul Jain, Namrata O’Dowd, Frank Paul, Toby Kashanin, Dmitry Gerard, Valerie A Gun’ko, Yurii K Prina-Mello, Adriele Volkov, Yuri |
author_facet | Samuel, Stephen Paul Jain, Namrata O’Dowd, Frank Paul, Toby Kashanin, Dmitry Gerard, Valerie A Gun’ko, Yurii K Prina-Mello, Adriele Volkov, Yuri |
author_sort | Samuel, Stephen Paul |
collection | PubMed |
description | Vascular endothelium is a potential target for therapeutic intervention in diverse pathological processes, including inflammation, atherosclerosis, and thrombosis. By virtue of their intravascular topography, endothelial cells are exposed to dynamically changing mechanical forces that are generated by blood flow. In the present study, we investigated the interactions of negatively charged 2.7 nm and 4.7 nm CdTe quantum dots and 50 nm silica particles with cultured endothelial cells under regulated shear stress (SS) conditions. Cultured cells within the engineered microfluidic channels were exposed to nanoparticles under static condition or under low, medium, and high SS rates (0.05, 0.1, and 0.5 Pa, respectively). Vascular inflammation and associated endothelial damage were simulated by treatment with tumor necrosis factor-α (TNF-α) or by compromising the cell membrane with the use of low Triton X-100 concentration. Our results demonstrate that SS is critical for nanoparticle uptake by endothelial cells. Maximal uptake was registered at the SS rate of 0.05 Pa. By contrast, endothelial exposure to mild detergents or TNF-α treatment had no significant effect on nanoparticle uptake. Atomic force microscopy demonstrated the increased formation of actin-based cytoskeletal structures, including stress fibers and membrane ruffles, which have been associated with nanoparticle endocytosis. In conclusion, the combinatorial effects of SS rates, vascular endothelial conditions, and nanoparticle physical and chemical properties must be taken into account for the successful design of nanoparticle–drug conjugates intended for parenteral delivery. |
format | Online Article Text |
id | pubmed-3384367 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-33843672012-06-28 Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow Samuel, Stephen Paul Jain, Namrata O’Dowd, Frank Paul, Toby Kashanin, Dmitry Gerard, Valerie A Gun’ko, Yurii K Prina-Mello, Adriele Volkov, Yuri Int J Nanomedicine Original Research Vascular endothelium is a potential target for therapeutic intervention in diverse pathological processes, including inflammation, atherosclerosis, and thrombosis. By virtue of their intravascular topography, endothelial cells are exposed to dynamically changing mechanical forces that are generated by blood flow. In the present study, we investigated the interactions of negatively charged 2.7 nm and 4.7 nm CdTe quantum dots and 50 nm silica particles with cultured endothelial cells under regulated shear stress (SS) conditions. Cultured cells within the engineered microfluidic channels were exposed to nanoparticles under static condition or under low, medium, and high SS rates (0.05, 0.1, and 0.5 Pa, respectively). Vascular inflammation and associated endothelial damage were simulated by treatment with tumor necrosis factor-α (TNF-α) or by compromising the cell membrane with the use of low Triton X-100 concentration. Our results demonstrate that SS is critical for nanoparticle uptake by endothelial cells. Maximal uptake was registered at the SS rate of 0.05 Pa. By contrast, endothelial exposure to mild detergents or TNF-α treatment had no significant effect on nanoparticle uptake. Atomic force microscopy demonstrated the increased formation of actin-based cytoskeletal structures, including stress fibers and membrane ruffles, which have been associated with nanoparticle endocytosis. In conclusion, the combinatorial effects of SS rates, vascular endothelial conditions, and nanoparticle physical and chemical properties must be taken into account for the successful design of nanoparticle–drug conjugates intended for parenteral delivery. Dove Medical Press 2012 2012-06-14 /pmc/articles/PMC3384367/ /pubmed/22745555 http://dx.doi.org/10.2147/IJN.S30624 Text en © 2012 Samuel et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Original Research Samuel, Stephen Paul Jain, Namrata O’Dowd, Frank Paul, Toby Kashanin, Dmitry Gerard, Valerie A Gun’ko, Yurii K Prina-Mello, Adriele Volkov, Yuri Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow |
title | Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow |
title_full | Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow |
title_fullStr | Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow |
title_full_unstemmed | Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow |
title_short | Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow |
title_sort | multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384367/ https://www.ncbi.nlm.nih.gov/pubmed/22745555 http://dx.doi.org/10.2147/IJN.S30624 |
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