The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles

Tony Bewersdorff,1 Jonathan Vonnemann,2 Asiye Kanik,1 Rainer Haag,2 Andrea Haase1 1Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Berlin, Germany; 2Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany Abstract:...

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Autores principales:	Bewersdorff T, Vonnemann J, Kanik A, Haag R, Haase A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	sulphated dendritic polyglycerols protein corona cellular uptake uptake receptors clathrin-mediated endocytosis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7858d2c49bf140bfa7fc2ca2696f4e70
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spelling	oai:doaj.org-article:7858d2c49bf140bfa7fc2ca2696f4e702021-12-02T05:02:16ZThe influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles1178-2013https://doaj.org/article/7858d2c49bf140bfa7fc2ca2696f4e702017-03-01T00:00:00Zhttps://www.dovepress.com/the-influence--of-surface-charge-on-serum-protein-interaction-and-cell-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tony Bewersdorff,1 Jonathan Vonnemann,2 Asiye Kanik,1 Rainer Haag,2 Andrea Haase1 1Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Berlin, Germany; 2Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany Abstract: Nanoparticles (NPs) have gained huge interest in the medical field, in particular for drug delivery purposes. However, binding of proteins often leads to fast NP uptake and rapid clearance, thereby hampering medical applications. Thus, it is essential to determine and control the bio–nano interface. This study investigated the serum protein interactions of dendritic polyglycerols (dPGs), which are promising drug delivery candidates by means of two dimensional gel electrophoresis (2DE) in combination with mass spectrometry. In order to investigate the influence of surface charge, sulfated (sulfated dendritic polyglycerol [dPGS]) and non-sulfated (dPGOH) surfaces were applied, which were synthesized on a gold core allowing for easier separation from unbound biomolecules through centrifugation. Furthermore, two different sizes for dPGS were included. Although size had only a minor influence, considerable differences were detected in protein affinity for dPGS versus dPGOH surfaces, with dPGOH binding much less proteins. Cellular uptake into human CD14+ monocytes was analyzed by flow cytometry, and dPGOH was taken up to a much lower extent compared to dPGS. By using a pull-down approach, possible cellular interaction partners of serum pre-incubated dPGS-Au20 NPs from the membrane fraction of THP-1 cells could be identified such as for instance the transferrin receptor or an integrin. Clathrin-mediated endocytosis was further investigated using chlorpromazine as an inhibitor, which resulted in a 50% decrease of the cellular uptake of dPGS. This study could confirm the influence of surface charge on protein interactions and cellular uptake of dPGS. Furthermore, the approach allowed for the identification of possible uptake receptors and insights into the uptake mechanism. Keywords: sulfated dendritic polyglycerols, protein corona, cellular uptake, uptake receptors, clathrin-mediated endocytosisBewersdorff TVonnemann JKanik AHaag RHaase ADove Medical Pressarticlesulphated dendritic polyglycerolsprotein coronacellular uptakeuptake receptorsclathrin-mediated endocytosisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2001-2019 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	sulphated dendritic polyglycerols protein corona cellular uptake uptake receptors clathrin-mediated endocytosis Medicine (General) R5-920
spellingShingle	sulphated dendritic polyglycerols protein corona cellular uptake uptake receptors clathrin-mediated endocytosis Medicine (General) R5-920 Bewersdorff T Vonnemann J Kanik A Haag R Haase A The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles
description	Tony Bewersdorff,1 Jonathan Vonnemann,2 Asiye Kanik,1 Rainer Haag,2 Andrea Haase1 1Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Berlin, Germany; 2Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany Abstract: Nanoparticles (NPs) have gained huge interest in the medical field, in particular for drug delivery purposes. However, binding of proteins often leads to fast NP uptake and rapid clearance, thereby hampering medical applications. Thus, it is essential to determine and control the bio–nano interface. This study investigated the serum protein interactions of dendritic polyglycerols (dPGs), which are promising drug delivery candidates by means of two dimensional gel electrophoresis (2DE) in combination with mass spectrometry. In order to investigate the influence of surface charge, sulfated (sulfated dendritic polyglycerol [dPGS]) and non-sulfated (dPGOH) surfaces were applied, which were synthesized on a gold core allowing for easier separation from unbound biomolecules through centrifugation. Furthermore, two different sizes for dPGS were included. Although size had only a minor influence, considerable differences were detected in protein affinity for dPGS versus dPGOH surfaces, with dPGOH binding much less proteins. Cellular uptake into human CD14+ monocytes was analyzed by flow cytometry, and dPGOH was taken up to a much lower extent compared to dPGS. By using a pull-down approach, possible cellular interaction partners of serum pre-incubated dPGS-Au20 NPs from the membrane fraction of THP-1 cells could be identified such as for instance the transferrin receptor or an integrin. Clathrin-mediated endocytosis was further investigated using chlorpromazine as an inhibitor, which resulted in a 50% decrease of the cellular uptake of dPGS. This study could confirm the influence of surface charge on protein interactions and cellular uptake of dPGS. Furthermore, the approach allowed for the identification of possible uptake receptors and insights into the uptake mechanism. Keywords: sulfated dendritic polyglycerols, protein corona, cellular uptake, uptake receptors, clathrin-mediated endocytosis
format	article
author	Bewersdorff T Vonnemann J Kanik A Haag R Haase A
author_facet	Bewersdorff T Vonnemann J Kanik A Haag R Haase A
author_sort	Bewersdorff T
title	The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles
title_short	The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles
title_full	The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles
title_fullStr	The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles
title_full_unstemmed	The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles
title_sort	influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/7858d2c49bf140bfa7fc2ca2696f4e70
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The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles

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