Uncovering the Fate and Risks of Intravenously Injected Prussian Blue Nanoparticles in mice by an Integrated Methodology of Toxicology, Pharmacokinetics, Proteomics, and Metabolomics

Abstract Background Prussian blue (PB) nanoparticles (NPs) have been intensively investigated for medical applications, but an in-depth toxicological investigation of PB NPs has not been implemented. In the present study, a comprehensive investigation of the fate and risks of PB NPs after intravenou...

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Main Authors: Haijing Qu, Xing Jin, Wei Cheng, Dongqi Wu, Boyu Ma, Chenmei Lou, Jian Zheng, Lijia Jing, Xiangdong Xue, Yang Wang
Format: Article
Language:English
Published: BMC 2023-05-01
Series:Particle and Fibre Toxicology
Subjects:
Online Access:https://doi.org/10.1186/s12989-023-00529-7
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author Haijing Qu
Xing Jin
Wei Cheng
Dongqi Wu
Boyu Ma
Chenmei Lou
Jian Zheng
Lijia Jing
Xiangdong Xue
Yang Wang
author_facet Haijing Qu
Xing Jin
Wei Cheng
Dongqi Wu
Boyu Ma
Chenmei Lou
Jian Zheng
Lijia Jing
Xiangdong Xue
Yang Wang
author_sort Haijing Qu
collection DOAJ
description Abstract Background Prussian blue (PB) nanoparticles (NPs) have been intensively investigated for medical applications, but an in-depth toxicological investigation of PB NPs has not been implemented. In the present study, a comprehensive investigation of the fate and risks of PB NPs after intravenous administration was carried out by using a mouse model and an integrated methodology of pharmacokinetics, toxicology, proteomics, and metabolomics. Results General toxicological studies demonstrated that intravenous administration of PB NPs at 5 or 10 mg/kg could not induce obvious toxicity in mice, while mice treated with a relatively high dose of PB NPs at 20 mg/kg exhibited loss of appetite and weight decrease in the first two days postinjection. Pharmacokinetic studies revealed that intravenously administered PB NPs (20 mg/kg) underwent fast clearance from blood, highly accumulated in the liver and lungs of mice, and finally cleared from tissues. By further integrated proteomics and metabolomics analysis, we found that protein expression and metabolite levels changed significantly in the liver and lungs of mice due to the high accumulation of PB NPs, leading to slight inflammatory responses and intracellular oxidative stress. Conclusions Collectively, our integrated experimental data imply that the high accumulation of PB NPs may cause potential risks to the liver and lungs of mice, which will provide detailed references and guidance for further clinical application of PB NPs in the future.
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spelling doaj.art-58cb4d00b91c467797caafcc3f23635f2023-05-07T11:03:29ZengBMCParticle and Fibre Toxicology1743-89772023-05-0120111410.1186/s12989-023-00529-7Uncovering the Fate and Risks of Intravenously Injected Prussian Blue Nanoparticles in mice by an Integrated Methodology of Toxicology, Pharmacokinetics, Proteomics, and MetabolomicsHaijing Qu0Xing Jin1Wei Cheng2Dongqi Wu3Boyu Ma4Chenmei Lou5Jian Zheng6Lijia Jing7Xiangdong Xue8Yang Wang9School of Life Science, Northeast Forestry UniversitySchool of Life Science, Northeast Forestry UniversitySchool of Pharmacy, Shanghai Frontiers Science Center for Drug Target Identification and Drug Delivery, Shanghai Jiao Tong UniversitySchool of Life Science, Northeast Forestry UniversitySchool of Life Science, Northeast Forestry UniversitySchool of Life Science, Northeast Forestry UniversitySchool of Life Science, Northeast Forestry UniversitySchool of Life Science, Northeast Forestry UniversitySchool of Pharmacy, Shanghai Frontiers Science Center for Drug Target Identification and Drug Delivery, Shanghai Jiao Tong UniversitySchool of Life Science, Northeast Forestry UniversityAbstract Background Prussian blue (PB) nanoparticles (NPs) have been intensively investigated for medical applications, but an in-depth toxicological investigation of PB NPs has not been implemented. In the present study, a comprehensive investigation of the fate and risks of PB NPs after intravenous administration was carried out by using a mouse model and an integrated methodology of pharmacokinetics, toxicology, proteomics, and metabolomics. Results General toxicological studies demonstrated that intravenous administration of PB NPs at 5 or 10 mg/kg could not induce obvious toxicity in mice, while mice treated with a relatively high dose of PB NPs at 20 mg/kg exhibited loss of appetite and weight decrease in the first two days postinjection. Pharmacokinetic studies revealed that intravenously administered PB NPs (20 mg/kg) underwent fast clearance from blood, highly accumulated in the liver and lungs of mice, and finally cleared from tissues. By further integrated proteomics and metabolomics analysis, we found that protein expression and metabolite levels changed significantly in the liver and lungs of mice due to the high accumulation of PB NPs, leading to slight inflammatory responses and intracellular oxidative stress. Conclusions Collectively, our integrated experimental data imply that the high accumulation of PB NPs may cause potential risks to the liver and lungs of mice, which will provide detailed references and guidance for further clinical application of PB NPs in the future.https://doi.org/10.1186/s12989-023-00529-7Prussian blue nanoparticlesToxicologyPharmacokineticsProteomicsMetabolomics
spellingShingle Haijing Qu
Xing Jin
Wei Cheng
Dongqi Wu
Boyu Ma
Chenmei Lou
Jian Zheng
Lijia Jing
Xiangdong Xue
Yang Wang
Uncovering the Fate and Risks of Intravenously Injected Prussian Blue Nanoparticles in mice by an Integrated Methodology of Toxicology, Pharmacokinetics, Proteomics, and Metabolomics
Particle and Fibre Toxicology
Prussian blue nanoparticles
Toxicology
Pharmacokinetics
Proteomics
Metabolomics
title Uncovering the Fate and Risks of Intravenously Injected Prussian Blue Nanoparticles in mice by an Integrated Methodology of Toxicology, Pharmacokinetics, Proteomics, and Metabolomics
title_full Uncovering the Fate and Risks of Intravenously Injected Prussian Blue Nanoparticles in mice by an Integrated Methodology of Toxicology, Pharmacokinetics, Proteomics, and Metabolomics
title_fullStr Uncovering the Fate and Risks of Intravenously Injected Prussian Blue Nanoparticles in mice by an Integrated Methodology of Toxicology, Pharmacokinetics, Proteomics, and Metabolomics
title_full_unstemmed Uncovering the Fate and Risks of Intravenously Injected Prussian Blue Nanoparticles in mice by an Integrated Methodology of Toxicology, Pharmacokinetics, Proteomics, and Metabolomics
title_short Uncovering the Fate and Risks of Intravenously Injected Prussian Blue Nanoparticles in mice by an Integrated Methodology of Toxicology, Pharmacokinetics, Proteomics, and Metabolomics
title_sort uncovering the fate and risks of intravenously injected prussian blue nanoparticles in mice by an integrated methodology of toxicology pharmacokinetics proteomics and metabolomics
topic Prussian blue nanoparticles
Toxicology
Pharmacokinetics
Proteomics
Metabolomics
url https://doi.org/10.1186/s12989-023-00529-7
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