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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Main Authors: Anna L. Brown, Marc P. Kai, Allison N. DuRoss, Gaurav Sahay, Conroy Sun
Format: Article
Language:English
Published: MDPI AG 2018-06-01
Series:Nanomaterials
Subjects:
Online Access:http://www.mdpi.com/2079-4991/8/6/410
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spelling doaj-7ec3aaf3d3b14f809997ba0c25481e072020-11-24T21:35:14ZengMDPI AGNanomaterials2079-49912018-06-018641010.3390/nano8060410nano8060410Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous AdministrationAnna L. Brown0Marc P. Kai1Allison N. DuRoss2Gaurav Sahay3Conroy Sun4Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Ave, Portland, OR 97201, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Ave, Portland, OR 97201, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Ave, Portland, OR 97201, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Ave, Portland, OR 97201, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Ave, Portland, OR 97201, USAPlatinum 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.http://www.mdpi.com/2079-4991/8/6/410platinumnanoparticlenoble metal nanoparticlesin vivo toxicitybioaccumulation
collection DOAJ
language English
format Article
sources DOAJ
author Anna L. Brown
Marc P. Kai
Allison N. DuRoss
Gaurav Sahay
Conroy Sun
spellingShingle Anna L. Brown
Marc P. Kai
Allison N. DuRoss
Gaurav Sahay
Conroy Sun
Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous Administration
Nanomaterials
platinum
nanoparticle
noble metal nanoparticles
in vivo toxicity
bioaccumulation
author_facet Anna L. Brown
Marc P. Kai
Allison N. DuRoss
Gaurav Sahay
Conroy Sun
author_sort Anna L. Brown
title 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_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_sort biodistribution and toxicity of micellar platinum nanoparticles in mice via intravenous administration
publisher MDPI AG
series Nanomaterials
issn 2079-4991
publishDate 2018-06-01
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.
topic platinum
nanoparticle
noble metal nanoparticles
in vivo toxicity
bioaccumulation
url http://www.mdpi.com/2079-4991/8/6/410
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