Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer

Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular biomolecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabil...

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Autores principales:	Rossana Terracciano, Yareli Carcamo-Bahena, E. Brian Butler, Danilo Demarchi, Alessandro Grattoni, Carly S. Filgueira
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	gold nanoparticles hyaluronate-thiol in vitro in vivo peritumoral cancer Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9edf1c1b219640d6b35e7ea55206adf9
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spelling	oai:doaj.org-article:9edf1c1b219640d6b35e7ea55206adf92021-11-25T16:49:02ZHyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer10.3390/biomedicines91115612227-9059https://doaj.org/article/9edf1c1b219640d6b35e7ea55206adf92021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1561https://doaj.org/toc/2227-9059Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular biomolecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired macrophage-driven clearance, consequently causing failed delivery of a targeted drug cargo. Hyaluronic acid (HA) is a bioactive, natural mucopolysaccharide with excellent antifouling properties, arising from its hydrophilic and polyanionic characteristics in physiological environments which prevent opsonization. In this study, hyaluronate-thiol (HA-SH) (MW 10 kDa) was used to surface-passivate gold nanoparticles (GNPs) synthesized using a citrate reduction method. HA functionalized GNP complexes (HA-GNPs) were characterized using absorption spectroscopy, scanning electron microscopy, zeta potential, and dynamic light scattering. GNP cellular uptake and potential dose-dependent cytotoxic effects due to treatment were evaluated in vitro in HeLa cells using inductively coupled plasma—optical emission spectrometry (ICP-OES) and trypan blue and MTT assays. Further, we quantified the in vivo biodistribution of intratumorally injected HA functionalized GNPs in Lewis Lung carcinoma (LLC) solid tumors grown on the flank of C57BL/6 mice and compared localization and retention with nascent particles. Our results reveal that HA-GNPs show overall greater peritumoral distribution (** <i>p</i> < 0.005, 3 days post-intratumoral injection) than citrate-GNPs with reduced biodistribution in off-target organs. This property represents an advantageous step forward in localized delivery of metal nano-complexes to the infiltrative region of a tumor, which may improve the application of nanomedicine in the diagnosis and treatment of cancer.Rossana TerraccianoYareli Carcamo-BahenaE. Brian ButlerDanilo DemarchiAlessandro GrattoniCarly S. FilgueiraMDPI AGarticlegold nanoparticleshyaluronate-thiolin vitroin vivoperitumoralcancerBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1561, p 1561 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gold nanoparticles hyaluronate-thiol in vitro in vivo peritumoral cancer Biology (General) QH301-705.5
spellingShingle	gold nanoparticles hyaluronate-thiol in vitro in vivo peritumoral cancer Biology (General) QH301-705.5 Rossana Terracciano Yareli Carcamo-Bahena E. Brian Butler Danilo Demarchi Alessandro Grattoni Carly S. Filgueira Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer
description	Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular biomolecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired macrophage-driven clearance, consequently causing failed delivery of a targeted drug cargo. Hyaluronic acid (HA) is a bioactive, natural mucopolysaccharide with excellent antifouling properties, arising from its hydrophilic and polyanionic characteristics in physiological environments which prevent opsonization. In this study, hyaluronate-thiol (HA-SH) (MW 10 kDa) was used to surface-passivate gold nanoparticles (GNPs) synthesized using a citrate reduction method. HA functionalized GNP complexes (HA-GNPs) were characterized using absorption spectroscopy, scanning electron microscopy, zeta potential, and dynamic light scattering. GNP cellular uptake and potential dose-dependent cytotoxic effects due to treatment were evaluated in vitro in HeLa cells using inductively coupled plasma—optical emission spectrometry (ICP-OES) and trypan blue and MTT assays. Further, we quantified the in vivo biodistribution of intratumorally injected HA functionalized GNPs in Lewis Lung carcinoma (LLC) solid tumors grown on the flank of C57BL/6 mice and compared localization and retention with nascent particles. Our results reveal that HA-GNPs show overall greater peritumoral distribution (** <i>p</i> < 0.005, 3 days post-intratumoral injection) than citrate-GNPs with reduced biodistribution in off-target organs. This property represents an advantageous step forward in localized delivery of metal nano-complexes to the infiltrative region of a tumor, which may improve the application of nanomedicine in the diagnosis and treatment of cancer.
format	article
author	Rossana Terracciano Yareli Carcamo-Bahena E. Brian Butler Danilo Demarchi Alessandro Grattoni Carly S. Filgueira
author_facet	Rossana Terracciano Yareli Carcamo-Bahena E. Brian Butler Danilo Demarchi Alessandro Grattoni Carly S. Filgueira
author_sort	Rossana Terracciano
title	Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer
title_short	Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer
title_full	Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer
title_fullStr	Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer
title_full_unstemmed	Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer
title_sort	hyaluronate-thiol passivation enhances gold nanoparticle peritumoral distribution when administered intratumorally in lung cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9edf1c1b219640d6b35e7ea55206adf9
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Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer

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