Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics

Abstract Background Nanoparticles have been utilized in brain research and therapeutics, including imaging, diagnosis, and drug delivery, owing to their versatile properties compared to bulk materials. However, exposure to nanoparticles leads to their accumulation in the brain, but drug development...

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Autores principales:	Tae Hwan Shin, Balachandran Manavalan, Da Yeon Lee, Shaherin Basith, Chan Seo, Man Jeong Paik, Sang-Wook Kim, Haewoon Seo, Ju Yeon Lee, Jin Young Kim, A Young Kim, Jee Min Chung, Eun Joo Baik, Seong Ho Kang, Dong-Kug Choi, Yup Kang, M. Maral Mouradian, Gwang Lee
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Silica-coated magnetic nanoparticles Nanotoxicity Integrated omics Microglia Machine learning Toxicology. Poisons RA1190-1270 Industrial hygiene. Industrial welfare HD7260-7780.8
Acceso en línea:	https://doaj.org/article/5a3f65fab7ff4f3ea7bfc98a0d28a485
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spelling	oai:doaj.org-article:5a3f65fab7ff4f3ea7bfc98a0d28a4852021-11-28T12:14:19ZSilica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics10.1186/s12989-021-00433-y1743-8977https://doaj.org/article/5a3f65fab7ff4f3ea7bfc98a0d28a4852021-11-01T00:00:00Zhttps://doi.org/10.1186/s12989-021-00433-yhttps://doaj.org/toc/1743-8977Abstract Background Nanoparticles have been utilized in brain research and therapeutics, including imaging, diagnosis, and drug delivery, owing to their versatile properties compared to bulk materials. However, exposure to nanoparticles leads to their accumulation in the brain, but drug development to counteract this nanotoxicity remains challenging. To date, concerns have risen about the potential toxicity to the brain associated with nanoparticles exposure via penetration of the brain blood barrier to address this issue. Methods Here the effect of silica-coated-magnetic nanoparticles containing the rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] were assessed on microglia through toxicological investigation, including biological analysis and integration of transcriptomics, proteomics, and metabolomics. MNPs@SiO2(RITC)-induced biological changes, such as morphology, generation of reactive oxygen species, intracellular accumulation of MNPs@SiO2(RITC) using transmission electron microscopy, and glucose uptake efficiency, were analyzed in BV2 murine microglial cells. Each omics data was collected via RNA-sequencing-based transcriptome analysis, liquid chromatography-tandem mass spectrometry-based proteome analysis, and gas chromatography- tandem mass spectrometry-based metabolome analysis. The three omics datasets were integrated and generated as a single network using a machine learning algorithm. Nineteen compounds were screened and predicted their effects on nanotoxicity within the triple-omics network. Results Intracellular reactive oxygen species production, an inflammatory response, and morphological activation of cells were greater, but glucose uptake was lower in MNPs@SiO2(RITC)-treated BV2 microglia and primary rat microglia in a dose-dependent manner. Expression of 121 genes (from 41,214 identified genes), and levels of 45 proteins (from 5918 identified proteins) and 17 metabolites (from 47 identified metabolites) related to the above phenomena changed in MNPs@SiO2(RITC)-treated microglia. A combination of glutathione and citrate attenuated nanotoxicity induced by MNPs@SiO2(RITC) and ten other nanoparticles in vitro and in the murine brain, protecting mostly the hippocampus and thalamus. Conclusions Combination of glutathione and citrate can be one of the candidates for nanotoxicity alleviating drug against MNPs@SiO2(RITC) induced detrimental effect, including elevation of intracellular reactive oxygen species level, activation of microglia, and reduction in glucose uptake efficiency. In addition, our findings indicate that an integrated triple omics approach provides useful and sensitive toxicological assessment for nanoparticles and screening of drug for nanotoxicity. Graphical AbstractTae Hwan ShinBalachandran ManavalanDa Yeon LeeShaherin BasithChan SeoMan Jeong PaikSang-Wook KimHaewoon SeoJu Yeon LeeJin Young KimA Young KimJee Min ChungEun Joo BaikSeong Ho KangDong-Kug ChoiYup KangM. Maral MouradianGwang LeeBMCarticleSilica-coated magnetic nanoparticlesNanotoxicityIntegrated omicsMicrogliaMachine learningToxicology. PoisonsRA1190-1270Industrial hygiene. Industrial welfareHD7260-7780.8ENParticle and Fibre Toxicology, Vol 18, Iss 1, Pp 1-24 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Silica-coated magnetic nanoparticles Nanotoxicity Integrated omics Microglia Machine learning Toxicology. Poisons RA1190-1270 Industrial hygiene. Industrial welfare HD7260-7780.8
spellingShingle	Silica-coated magnetic nanoparticles Nanotoxicity Integrated omics Microglia Machine learning Toxicology. Poisons RA1190-1270 Industrial hygiene. Industrial welfare HD7260-7780.8 Tae Hwan Shin Balachandran Manavalan Da Yeon Lee Shaherin Basith Chan Seo Man Jeong Paik Sang-Wook Kim Haewoon Seo Ju Yeon Lee Jin Young Kim A Young Kim Jee Min Chung Eun Joo Baik Seong Ho Kang Dong-Kug Choi Yup Kang M. Maral Mouradian Gwang Lee Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics
description	Abstract Background Nanoparticles have been utilized in brain research and therapeutics, including imaging, diagnosis, and drug delivery, owing to their versatile properties compared to bulk materials. However, exposure to nanoparticles leads to their accumulation in the brain, but drug development to counteract this nanotoxicity remains challenging. To date, concerns have risen about the potential toxicity to the brain associated with nanoparticles exposure via penetration of the brain blood barrier to address this issue. Methods Here the effect of silica-coated-magnetic nanoparticles containing the rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] were assessed on microglia through toxicological investigation, including biological analysis and integration of transcriptomics, proteomics, and metabolomics. MNPs@SiO2(RITC)-induced biological changes, such as morphology, generation of reactive oxygen species, intracellular accumulation of MNPs@SiO2(RITC) using transmission electron microscopy, and glucose uptake efficiency, were analyzed in BV2 murine microglial cells. Each omics data was collected via RNA-sequencing-based transcriptome analysis, liquid chromatography-tandem mass spectrometry-based proteome analysis, and gas chromatography- tandem mass spectrometry-based metabolome analysis. The three omics datasets were integrated and generated as a single network using a machine learning algorithm. Nineteen compounds were screened and predicted their effects on nanotoxicity within the triple-omics network. Results Intracellular reactive oxygen species production, an inflammatory response, and morphological activation of cells were greater, but glucose uptake was lower in MNPs@SiO2(RITC)-treated BV2 microglia and primary rat microglia in a dose-dependent manner. Expression of 121 genes (from 41,214 identified genes), and levels of 45 proteins (from 5918 identified proteins) and 17 metabolites (from 47 identified metabolites) related to the above phenomena changed in MNPs@SiO2(RITC)-treated microglia. A combination of glutathione and citrate attenuated nanotoxicity induced by MNPs@SiO2(RITC) and ten other nanoparticles in vitro and in the murine brain, protecting mostly the hippocampus and thalamus. Conclusions Combination of glutathione and citrate can be one of the candidates for nanotoxicity alleviating drug against MNPs@SiO2(RITC) induced detrimental effect, including elevation of intracellular reactive oxygen species level, activation of microglia, and reduction in glucose uptake efficiency. In addition, our findings indicate that an integrated triple omics approach provides useful and sensitive toxicological assessment for nanoparticles and screening of drug for nanotoxicity. Graphical Abstract
format	article
author	Tae Hwan Shin Balachandran Manavalan Da Yeon Lee Shaherin Basith Chan Seo Man Jeong Paik Sang-Wook Kim Haewoon Seo Ju Yeon Lee Jin Young Kim A Young Kim Jee Min Chung Eun Joo Baik Seong Ho Kang Dong-Kug Choi Yup Kang M. Maral Mouradian Gwang Lee
author_facet	Tae Hwan Shin Balachandran Manavalan Da Yeon Lee Shaherin Basith Chan Seo Man Jeong Paik Sang-Wook Kim Haewoon Seo Ju Yeon Lee Jin Young Kim A Young Kim Jee Min Chung Eun Joo Baik Seong Ho Kang Dong-Kug Choi Yup Kang M. Maral Mouradian Gwang Lee
author_sort	Tae Hwan Shin
title	Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics
title_short	Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics
title_full	Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics
title_fullStr	Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics
title_full_unstemmed	Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics
title_sort	silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics
publisher	BMC
publishDate	2021
url	https://doaj.org/article/5a3f65fab7ff4f3ea7bfc98a0d28a485
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Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics

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