Back to Journals » International Journal of Nanomedicine » Volume 7

Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow

Authors Samuel SP, Jain N, O'Dowd F, Paul T, Kashanin D, Gerard VA, Gun'ko YK, Prina-Mello A, Volkov Y

Received 7 February 2012

Accepted for publication 21 March 2012

Published 14 June 2012 Volume 2012:7 Pages 2943—2956

DOI https://doi.org/10.2147/IJN.S30624

Review by Single-blind

Peer reviewer comments 3

Stephen Paul Samuel,1,* Namrata Jain,1,* Frank O’Dowd,2 Toby Paul,2 Dmitry Kashanin,2 Valerie A Gerard,3 Yurii K Gun’ko,3 Adriele Prina-Mello,1,4 Yuri Volkov,1,4
1Department of Clinical Medicine, Institute of Molecular Medicine, 2Cellix Ltd, Longmile Business Centre, 3School of Chemistry, 4Centre for Research on Adaptive Nanostructures and Nanodevices, Trinity College Dublin, Dublin, Ireland

*
These authors contributed equally to this work

Abstract: 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.

Keywords: endothelium, shear stress, quantum dots, membrane ruffling, stress fibers, atomic force microscopy, microfluidics

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Optimal delivery of male breast cancer follow-up care: improving outcomes

Ferzoco RM, Ruddy KJ

Breast Cancer: Targets and Therapy 2015, 7:371-379

Published Date: 23 November 2015

Advances in cancer pain from bone metastasis

Zhu XC, Zhang JL, Ge CT, Yu YY, Wang P, Yuan TF, Fu CY

Drug Design, Development and Therapy 2015, 9:4239-4245

Published Date: 18 August 2015

Breast cancer causes and treatment: where are we going wrong?

Seymour CB, Mothersill C

Breast Cancer: Targets and Therapy 2013, 5:111-119

Published Date: 3 December 2013

Update of research on the role of EZH2 in cancer progression

Shen L, Cui J, Liang S, Pang Y, Liu P

OncoTargets and Therapy 2013, 6:321-324

Published Date: 4 April 2013

Capecitabine in the management of colorectal cancer

Hirsch BR, Zafar SY

Cancer Management and Research 2011, 3:79-89

Published Date: 24 March 2011