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Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous Administration

Platinum nanoparticles (PtNPs) have shown promise as diagnostic and therapeutic agents due to their unique physiochemical properties. However, critical parameters, such as toxicity and accumulation at both desired and other tissues, remain a significant concern in the clinical translation of these n...

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Autores principales: Brown, Anna L., Kai, Marc P., DuRoss, Allison N., Sahay, Gaurav, Sun, Conroy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027383/
https://www.ncbi.nlm.nih.gov/pubmed/29875350
http://dx.doi.org/10.3390/nano8060410
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author Brown, Anna L.
Kai, Marc P.
DuRoss, Allison N.
Sahay, Gaurav
Sun, Conroy
author_facet Brown, Anna L.
Kai, Marc P.
DuRoss, Allison N.
Sahay, Gaurav
Sun, Conroy
author_sort Brown, Anna L.
collection PubMed
description Platinum nanoparticles (PtNPs) have shown promise as diagnostic and therapeutic agents due to their unique physiochemical properties. However, critical parameters, such as toxicity and accumulation at both desired and other tissues, remain a significant concern in the clinical translation of these nanomaterials. Here, we examine the cytotoxicity, biodistribution, and effect on clearance organ function of an intravenously administered polyethylene glycol (PEG) -ylated PtNP construct. We synthesized hydrophobic PtNPs and assembled them into aqueous micelles with the lipid-polymer conjugate 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-PEG (PtNP: DSPE-PEG, ~70 nm). This construct was well tolerated in mice receiving up to 15 mg platinum per kg body weight with no observed loss in weight, plasma chemistry within normal healthy ranges, and normal histopathology of organs after three weeks. Platinum quantification studies (inductively-coupled plasma mass spectroscopy (ICP-MS)) were also performed to assess biodistribution of PtNPs. The findings of this study are consistent with the in vivo accumulation of metal nanomaterials and further highlight the need to address clearance when designing nanomaterials for medical applications.
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spelling pubmed-60273832018-07-13 Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous Administration Brown, Anna L. Kai, Marc P. DuRoss, Allison N. Sahay, Gaurav Sun, Conroy Nanomaterials (Basel) Article Platinum nanoparticles (PtNPs) have shown promise as diagnostic and therapeutic agents due to their unique physiochemical properties. However, critical parameters, such as toxicity and accumulation at both desired and other tissues, remain a significant concern in the clinical translation of these nanomaterials. Here, we examine the cytotoxicity, biodistribution, and effect on clearance organ function of an intravenously administered polyethylene glycol (PEG) -ylated PtNP construct. We synthesized hydrophobic PtNPs and assembled them into aqueous micelles with the lipid-polymer conjugate 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-PEG (PtNP: DSPE-PEG, ~70 nm). This construct was well tolerated in mice receiving up to 15 mg platinum per kg body weight with no observed loss in weight, plasma chemistry within normal healthy ranges, and normal histopathology of organs after three weeks. Platinum quantification studies (inductively-coupled plasma mass spectroscopy (ICP-MS)) were also performed to assess biodistribution of PtNPs. The findings of this study are consistent with the in vivo accumulation of metal nanomaterials and further highlight the need to address clearance when designing nanomaterials for medical applications. MDPI 2018-06-07 /pmc/articles/PMC6027383/ /pubmed/29875350 http://dx.doi.org/10.3390/nano8060410 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brown, Anna L.
Kai, Marc P.
DuRoss, Allison N.
Sahay, Gaurav
Sun, Conroy
Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous Administration
title Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous Administration
title_full Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous Administration
title_fullStr Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous Administration
title_full_unstemmed Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous Administration
title_short Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous Administration
title_sort biodistribution and toxicity of micellar platinum nanoparticles in mice via intravenous administration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027383/
https://www.ncbi.nlm.nih.gov/pubmed/29875350
http://dx.doi.org/10.3390/nano8060410
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