Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

Ming J Cheng,1 Rajiv Kumar,2 Srinivas Sridhar,1–3 Thomas J Webster,1,4 Eno E Ebong1 1Department of Chemical Engineering, 2Department of Physics, Northeastern University, 3Department of Radiation Oncology, Harvard Medical School, Boston, MA, USA; 4Center of Excellence for Advanced Material...

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Autores principales:	Cheng MJ, Kumar R, Sridhar S, Webster TJ, Ebong EE
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Glycocalyx Heparan Sulfate Endothelial Cells Nanoparticle Gold Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/15d8fc296d864879b7de94d7828d6f1d
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spelling	oai:doaj.org-article:15d8fc296d864879b7de94d7828d6f1d2021-12-02T03:11:41ZEndothelial glycocalyx conditions influence nanoparticle uptake for passive targeting1178-2013https://doaj.org/article/15d8fc296d864879b7de94d7828d6f1d2016-07-01T00:00:00Zhttps://www.dovepress.com/endothelial-glycocalyx-conditions-influence-nanoparticle-uptake-for-pa-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ming J Cheng,1 Rajiv Kumar,2 Srinivas Sridhar,1–3 Thomas J Webster,1,4 Eno E Ebong1 1Department of Chemical Engineering, 2Department of Physics, Northeastern University, 3Department of Radiation Oncology, Harvard Medical School, Boston, MA, USA; 4Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Cardiovascular diseases are facilitated by endothelial cell (EC) dysfunction and coincide with EC glycocalyx coat shedding. These diseases may be prevented by delivering medications to affected vascular regions using circulating nanoparticle (NP) drug carriers. The objective of the present study was to observe how the delivery of 10 nm polyethylene glycol-coated gold NPs (PEG-AuNP) to ECs is impacted by glycocalyx structure on the EC surface. Rat fat pad endothelial cells were chosen for their robust glycocalyx, verified by fluorescent immunolabeling of adsorbed albumin and integrated heparan sulfate (HS) chains. Confocal fluorescent imaging revealed a ~3 µm thick glycocalyx layer, covering 75% of the ECs and containing abundant HS. This healthy glycocalyx hindered the uptake of PEG-AuNP as expected because glycocalyx pores are typically 7 nm wide. Additional glycocalyx models tested included: a collapsed glycocalyx obtained by culturing cells in reduced protein media, a degraded glycocalyx obtained by applying heparinase III enzyme to specifically cleave HS, and a recovered glycocalyx obtained by supplementing exogenous HS into the media after enzyme degradation. The collapsed glycocalyx was ~2 µm thick with unchanged EC coverage and sustained HS content. The degraded glycocalyx showed similar changes in EC thickness and coverage but its HS thickness was reduced to 0.7 µm and spanned only 10% of the original EC surface. Both dysfunctional models retained six- to sevenfold more PEG-AuNP compared to the healthy glycocalyx. The collapsed glycocalyx permitted NPs to cross the glycocalyx into intracellular spaces, whereas the degraded glycocalyx trapped the PEG-AuNP within the glycocalyx. The repaired glycocalyx model partially restored HS thickness to 1.2 µm and 44% coverage of the ECs, but it was able to reverse the NP uptake back to baseline levels. In summary, this study showed that the glycocalyx structure is critical for NP uptake by ECs and may serve as a passive pathway for delivering NPs to dysfunctional ECs. Keywords: glycocalyx, heparan sulfate, endothelial cells, NP, goldCheng MJKumar RSridhar SWebster TJEbong EEDove Medical PressarticleGlycocalyxHeparan SulfateEndothelial CellsNanoparticleGoldMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 3305-3315 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Glycocalyx Heparan Sulfate Endothelial Cells Nanoparticle Gold Medicine (General) R5-920
spellingShingle	Glycocalyx Heparan Sulfate Endothelial Cells Nanoparticle Gold Medicine (General) R5-920 Cheng MJ Kumar R Sridhar S Webster TJ Ebong EE Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting
description	Ming J Cheng,1 Rajiv Kumar,2 Srinivas Sridhar,1–3 Thomas J Webster,1,4 Eno E Ebong1 1Department of Chemical Engineering, 2Department of Physics, Northeastern University, 3Department of Radiation Oncology, Harvard Medical School, Boston, MA, USA; 4Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Cardiovascular diseases are facilitated by endothelial cell (EC) dysfunction and coincide with EC glycocalyx coat shedding. These diseases may be prevented by delivering medications to affected vascular regions using circulating nanoparticle (NP) drug carriers. The objective of the present study was to observe how the delivery of 10 nm polyethylene glycol-coated gold NPs (PEG-AuNP) to ECs is impacted by glycocalyx structure on the EC surface. Rat fat pad endothelial cells were chosen for their robust glycocalyx, verified by fluorescent immunolabeling of adsorbed albumin and integrated heparan sulfate (HS) chains. Confocal fluorescent imaging revealed a ~3 µm thick glycocalyx layer, covering 75% of the ECs and containing abundant HS. This healthy glycocalyx hindered the uptake of PEG-AuNP as expected because glycocalyx pores are typically 7 nm wide. Additional glycocalyx models tested included: a collapsed glycocalyx obtained by culturing cells in reduced protein media, a degraded glycocalyx obtained by applying heparinase III enzyme to specifically cleave HS, and a recovered glycocalyx obtained by supplementing exogenous HS into the media after enzyme degradation. The collapsed glycocalyx was ~2 µm thick with unchanged EC coverage and sustained HS content. The degraded glycocalyx showed similar changes in EC thickness and coverage but its HS thickness was reduced to 0.7 µm and spanned only 10% of the original EC surface. Both dysfunctional models retained six- to sevenfold more PEG-AuNP compared to the healthy glycocalyx. The collapsed glycocalyx permitted NPs to cross the glycocalyx into intracellular spaces, whereas the degraded glycocalyx trapped the PEG-AuNP within the glycocalyx. The repaired glycocalyx model partially restored HS thickness to 1.2 µm and 44% coverage of the ECs, but it was able to reverse the NP uptake back to baseline levels. In summary, this study showed that the glycocalyx structure is critical for NP uptake by ECs and may serve as a passive pathway for delivering NPs to dysfunctional ECs. Keywords: glycocalyx, heparan sulfate, endothelial cells, NP, gold
format	article
author	Cheng MJ Kumar R Sridhar S Webster TJ Ebong EE
author_facet	Cheng MJ Kumar R Sridhar S Webster TJ Ebong EE
author_sort	Cheng MJ
title	Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting
title_short	Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting
title_full	Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting
title_fullStr	Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting
title_full_unstemmed	Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting
title_sort	endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/15d8fc296d864879b7de94d7828d6f1d
work_keys_str_mv	AT chengmj endothelialglycocalyxconditionsinfluencenanoparticleuptakeforpassivetargeting AT kumarr endothelialglycocalyxconditionsinfluencenanoparticleuptakeforpassivetargeting AT sridhars endothelialglycocalyxconditionsinfluencenanoparticleuptakeforpassivetargeting AT webstertj endothelialglycocalyxconditionsinfluencenanoparticleuptakeforpassivetargeting AT ebongee endothelialglycocalyxconditionsinfluencenanoparticleuptakeforpassivetargeting
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Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

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