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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2018-06-01
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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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