Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells

Ming J Cheng,1,* Nandita N Bal,1,* Priya Prabakaran,1 Rajiv Kumar,2,3 Thomas J Webster,1,4 Srinivas Sridhar,1,2 Eno E Ebong1,2,5 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Department of Physics, Northeastern University, Boston, MA, USA; 3Millipore Sigma, Milwauk...

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Autores principales:	Cheng MJ, Bal NN, Prabakaran P, Kumar R, Webster TJ, Sridhar S, Ebong EE
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Human Endothelial Cells Gold Nanoparticles Nanorods Glycocalyx Heparan Sulfate Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b0568e87cea34ef4929561dd55f68cfb
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spelling	oai:doaj.org-article:b0568e87cea34ef4929561dd55f68cfb2021-12-02T04:17:31ZUltrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells1178-2013https://doaj.org/article/b0568e87cea34ef4929561dd55f68cfb2019-01-01T00:00:00Zhttps://www.dovepress.com/ultrasmall-gold-nanorods-synthesis-and-glycocalyx-related-permeability-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ming J Cheng,1,* Nandita N Bal,1,* Priya Prabakaran,1 Rajiv Kumar,2,3 Thomas J Webster,1,4 Srinivas Sridhar,1,2 Eno E Ebong1,2,5 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Department of Physics, Northeastern University, Boston, MA, USA; 3Millipore Sigma, Milwaukee, WI, USA; 4Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA *These authors contributed equally to this work Background: Clinical data show shed endothelial glycocalyx (GCX) components in blood samples of atherosclerotic patients, linking atherosclerotic development to endothelial GCX integrity. Healthy GCX has pores no >7 nm, and shed GCX has even larger pores. Therefore, we suggest targeting and treating atherosclerosis-prone blood vessels by using nanoscale vehicles to deliver drugs via the nanoscale GCX as it becomes dysfunctional. Materials and methods: To test our idea, we investigated permeability of nanoparticles in endothelium, as related to a GCX expression. The present work involves nanorods, which are expected to interact with larger portions of endothelial cell (EC) membranes, due to surface area of the nanorod long axis. Conventional nanorod diameters are orders of magnitude larger than the GCX pore size, so we adapted conventional synthesis methods to fabricate ultrasmall gold nanorods (GNRs). Our ultrasmall GNRs have an aspect ratio of 3.4, with a length of 27.9±3.1 nm and a diameter of 8.2±1.4 nm. In addition, we produced GNRs that are biocompatible and fluorescently visible, by coating the surface with functionalized polyethylene glycol and Alexa Fluor 647. To study GNR–GCX interactions, we used human ECs, for species relevance. Results: Under life-like flow conditions, the human ECs are densely covered with a 1.3 µm thick layer of GCX, which coincides with minimal GNR permeability. When the GCX is weakened from lack of flow (static culture) or the presence of GCX degradation enzyme in the flow stream, the GCX shows 40% and 60% decreased thickness, respectively. GCX weakness due to lack of flow only slightly increases cellular permeability to GNRs, while GCX weakness due to the presence of enzyme in the flow leads to substantial increase in GNR permeability. Conclusion: These results clarify that the GCX structure is an avenue through which drug-carrying nanoparticles can be delivered for targeting affected blood vessels to treat atherosclerosis. Keywords: human endothelial cells, gold nanoparticles, nanorods, glycocalyx, heparan sulfateCheng MJBal NNPrabakaran PKumar RWebster TJSridhar SEbong EEDove Medical PressarticleHuman Endothelial CellsGold NanoparticlesNanorodsGlycocalyxHeparan SulfateMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 319-333 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Human Endothelial Cells Gold Nanoparticles Nanorods Glycocalyx Heparan Sulfate Medicine (General) R5-920
spellingShingle	Human Endothelial Cells Gold Nanoparticles Nanorods Glycocalyx Heparan Sulfate Medicine (General) R5-920 Cheng MJ Bal NN Prabakaran P Kumar R Webster TJ Sridhar S Ebong EE Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells
description	Ming J Cheng,1,* Nandita N Bal,1,* Priya Prabakaran,1 Rajiv Kumar,2,3 Thomas J Webster,1,4 Srinivas Sridhar,1,2 Eno E Ebong1,2,5 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Department of Physics, Northeastern University, Boston, MA, USA; 3Millipore Sigma, Milwaukee, WI, USA; 4Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA *These authors contributed equally to this work Background: Clinical data show shed endothelial glycocalyx (GCX) components in blood samples of atherosclerotic patients, linking atherosclerotic development to endothelial GCX integrity. Healthy GCX has pores no >7 nm, and shed GCX has even larger pores. Therefore, we suggest targeting and treating atherosclerosis-prone blood vessels by using nanoscale vehicles to deliver drugs via the nanoscale GCX as it becomes dysfunctional. Materials and methods: To test our idea, we investigated permeability of nanoparticles in endothelium, as related to a GCX expression. The present work involves nanorods, which are expected to interact with larger portions of endothelial cell (EC) membranes, due to surface area of the nanorod long axis. Conventional nanorod diameters are orders of magnitude larger than the GCX pore size, so we adapted conventional synthesis methods to fabricate ultrasmall gold nanorods (GNRs). Our ultrasmall GNRs have an aspect ratio of 3.4, with a length of 27.9±3.1 nm and a diameter of 8.2±1.4 nm. In addition, we produced GNRs that are biocompatible and fluorescently visible, by coating the surface with functionalized polyethylene glycol and Alexa Fluor 647. To study GNR–GCX interactions, we used human ECs, for species relevance. Results: Under life-like flow conditions, the human ECs are densely covered with a 1.3 µm thick layer of GCX, which coincides with minimal GNR permeability. When the GCX is weakened from lack of flow (static culture) or the presence of GCX degradation enzyme in the flow stream, the GCX shows 40% and 60% decreased thickness, respectively. GCX weakness due to lack of flow only slightly increases cellular permeability to GNRs, while GCX weakness due to the presence of enzyme in the flow leads to substantial increase in GNR permeability. Conclusion: These results clarify that the GCX structure is an avenue through which drug-carrying nanoparticles can be delivered for targeting affected blood vessels to treat atherosclerosis. Keywords: human endothelial cells, gold nanoparticles, nanorods, glycocalyx, heparan sulfate
format	article
author	Cheng MJ Bal NN Prabakaran P Kumar R Webster TJ Sridhar S Ebong EE
author_facet	Cheng MJ Bal NN Prabakaran P Kumar R Webster TJ Sridhar S Ebong EE
author_sort	Cheng MJ
title	Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells
title_short	Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells
title_full	Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells
title_fullStr	Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells
title_full_unstemmed	Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells
title_sort	ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/b0568e87cea34ef4929561dd55f68cfb
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Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells

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