A tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size

Julian DS Willett, Marlon G Lawrence, Jennifer C Wilder, Oliver Smithies† Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA †Dr Oliver Smithies passed away on January 10, 2017 Abstract: In this study, we descri...

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Autores principales: Willett JDS, Lawrence MG, Wilder JC, Smithies O
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2017
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Acceso en línea:https://doaj.org/article/3a5053486a554a678a9cf6133e0b4ac5
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spelling oai:doaj.org-article:3a5053486a554a678a9cf6133e0b4ac52021-12-02T08:08:04ZA tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size1178-2013https://doaj.org/article/3a5053486a554a678a9cf6133e0b4ac52017-03-01T00:00:00Zhttps://www.dovepress.com/a-tetraethylene-glycol-coat-gives-gold-nanoparticles-long-in-vivo-half-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Julian DS Willett, Marlon G Lawrence, Jennifer C Wilder, Oliver Smithies† Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA †Dr Oliver Smithies passed away on January 10, 2017 Abstract: In this study, we describe the experiments determining whether coating gold nanoparticles with tetraethylene glycol (TEG) provides pharmacologically relevant advantages, such as increased serum half-life and resistance to protein adsorption. Monodisperse TEG-coated, NaBH4-reduced gold nanoparticles with a hydrodynamic size comparable to albumin were synthesized by reducing gold chloride with NaBH4 under alkaline conditions in the presence of TEG-SH. The particles were characterized by gel electrophoresis, column chromatography, and transmission electron microscopy. The nanoparticles were subsequently injected intravenously into mice, and their half-lives and final destinations were determined via photometric analysis, light microscopy (LM), and transmission electron microscopy. The TEG particles had a long half-life (~400 minutes) that was not influenced by splenectomy. After 500 minutes of injection, TEG particles were found in kidney proximal tubule cell vesicles and in spleen red and white pulp. The particles induced apoptosis in the spleen red pulp but not in white pulp or the kidney. Some of the TEG particles appeared to have undergone ligand exchange reactions that increased their charge. The TEG particles were shown to be resistant to nonspecific protein adsorption, as judged by gel electrophoresis and column chromatography. These results demonstrate that naturally monodisperse, small-sized gold nanoparticles coated with TEG have long in vivo plasma half-lives, are minimally toxic, and are resistant to protein adsorption. This suggests that a TEG coating should be considered as an alternative to a polyethylene glycol coating, which is polydisperse and of much larger size. Keywords: tetraethylene glycol, tetraethylene glycol coating, polyethylene glycol, splenectomy, spleen clearance, kidney clearanceWillett JDSLawrence MGWilder JCSmithies ODove Medical Pressarticletetraethylene glycolpolyethylene glycolglutathione coatingsplenectomyspleen uptakeMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2581-2592 (2017)
institution DOAJ
collection DOAJ
language EN
topic tetraethylene glycol
polyethylene glycol
glutathione coating
splenectomy
spleen uptake
Medicine (General)
R5-920
spellingShingle tetraethylene glycol
polyethylene glycol
glutathione coating
splenectomy
spleen uptake
Medicine (General)
R5-920
Willett JDS
Lawrence MG
Wilder JC
Smithies O
A tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size
description Julian DS Willett, Marlon G Lawrence, Jennifer C Wilder, Oliver Smithies† Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA †Dr Oliver Smithies passed away on January 10, 2017 Abstract: In this study, we describe the experiments determining whether coating gold nanoparticles with tetraethylene glycol (TEG) provides pharmacologically relevant advantages, such as increased serum half-life and resistance to protein adsorption. Monodisperse TEG-coated, NaBH4-reduced gold nanoparticles with a hydrodynamic size comparable to albumin were synthesized by reducing gold chloride with NaBH4 under alkaline conditions in the presence of TEG-SH. The particles were characterized by gel electrophoresis, column chromatography, and transmission electron microscopy. The nanoparticles were subsequently injected intravenously into mice, and their half-lives and final destinations were determined via photometric analysis, light microscopy (LM), and transmission electron microscopy. The TEG particles had a long half-life (~400 minutes) that was not influenced by splenectomy. After 500 minutes of injection, TEG particles were found in kidney proximal tubule cell vesicles and in spleen red and white pulp. The particles induced apoptosis in the spleen red pulp but not in white pulp or the kidney. Some of the TEG particles appeared to have undergone ligand exchange reactions that increased their charge. The TEG particles were shown to be resistant to nonspecific protein adsorption, as judged by gel electrophoresis and column chromatography. These results demonstrate that naturally monodisperse, small-sized gold nanoparticles coated with TEG have long in vivo plasma half-lives, are minimally toxic, and are resistant to protein adsorption. This suggests that a TEG coating should be considered as an alternative to a polyethylene glycol coating, which is polydisperse and of much larger size. Keywords: tetraethylene glycol, tetraethylene glycol coating, polyethylene glycol, splenectomy, spleen clearance, kidney clearance
format article
author Willett JDS
Lawrence MG
Wilder JC
Smithies O
author_facet Willett JDS
Lawrence MG
Wilder JC
Smithies O
author_sort Willett JDS
title A tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size
title_short A tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size
title_full A tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size
title_fullStr A tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size
title_full_unstemmed A tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size
title_sort tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/3a5053486a554a678a9cf6133e0b4ac5
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