The endocytic penetration mechanism of iron oxide magnetic nanoparticles with positively charged cover: A morphological approach

Cañete, Magdalena; Soriano, Joan Manuel; Villanueva, Ángeles; Roca, Alejandro G.; Veintemillas, S.; Serna, Carlos J.; Miranda, Rodolfo; Morales, M.P.

doi:10.3892/ijmm_00000496

Cited by 22 publications

(11 citation statements)

References 20 publications

(32 reference statements)

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“…This indicates once again the inverse toxicity of the FeNPs in cells of different functions. However, these genes demonstrated the endocytotic activity of two cells to the FeNPs, which agrees with the previous reports that the FeNPs were internalized into cells by endocytosis [54][55][56][57]. In addition to the phagosome pathway, the lysosome and notch signaling pathways were also enriched by the genes induced by ldFeNPs in the THP-1 cells ( Figure 10A).…”

Section: Pathway Analysis Of Fenp-responsive Genessupporting

confidence: 91%

Effects of an 11-nm DMSA-coated iron nanoparticle on the gene expression profile of two human cell lines, THP-1 and HepG2

Zhang¹,

Wang²,

Zou³

et al. 2016

Nano Online

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Background: Iron nanoparticles (FeNPs) have attracted increasing attention over the past two decades owing to their promising application as biomedical agents. However, to ensure safe application, their potential nanotoxicity should be carefully and thoroughly evaluated. Studies on the effects of FeNPs on cells at the transcriptomic level will be helpful for identifying any potential nanotoxicity of FeNPs and providing valuable mechanistic insights into various FeNPs-induced nanotoxicities. Results: This study investigated the effects of an 11-nm dimercaptosuccinic acid-coated magnetite nanoparticle on the gene expression profiles of two human cell lines, THP-1 and HepG2. It was found that the expression of hundreds of genes was significantly changed by a 24-h treatment with the nanoparticles at two doses, 50 μg/mL and 100 μg/mL, in the two cell types. By identifying the differentially expressed genes and annotating their functions, this study characterized the general and cell-specific effects of the nanoparticles on two cell types at the gene, biological process and pathway levels. At these doses, the overall effects of the nanoparticle on the THP-1 cells were the induction of various responses and repression of protein translation, but in the HepG2 cells, the main effects were the promotion of cell metabolism, growth and mobility. In combination with a previous study, this study also characterized the common genes, biological processes and pathways affected by the nanoparticle in two human and mouse cell lines and identified Id3 as a nanotoxicity biomarker of the nanoparticle. Conclusion: The studied FeNPs exerted significant effects on the gene expression profiles of human cells. These effects were highly dependent on the innate biological functions of cells, i.e., the cell types. However, cells can also show some cell type-independent effects such as repression of Id3 expression. Id3 can be used as a nanotoxicity biomarker for iron nanoparticles.

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Section: Pathway Analysis Of Fenp-responsive Genessupporting

confidence: 91%

Effects of an 11-nm DMSA-coated iron nanoparticle on the gene expression profile of two human cell lines, THP-1 and HepG2

Zhang¹,

Wang²,

Zou³

et al. 2016

Nano Online

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“…Previous studies on NP uptake reported on clathrin-dependent endocytosis mechanisms as well as internalization by the macropinocytosis pathway in iron oxide or silver nanoparticles. 42 There was a slightly enhanced CD 90 expression and decreased CD 73 expression after ZnO-NP exposure compared to the control, but differences were not significant. located in the perinuclear cytoplasm whereas an intranuclear distribution could only be observed sporadically.…”

Section: Discussionmentioning

confidence: 62%

Functional Responses of Human Adipose Tissue-Derived Mesenchymal Stem Cells to Metal Oxide Nanoparticles <I>In</I> <I>Vitro</I>

Hackenberg¹,

Scherzed²,

Technau³

et al. 2013

Journal of Biomedical Nanotechnology

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Nanoparticles (NPs) are frequently applied in biomedical applications. The use of human mesenchymal stem cells (hMSC) in biomedicine is pivotal, especially in oncology and tissue engineering. Titanium dioxide (TiO2) and zinc oxide (ZnO) NPs are interesting agents in experimental oncology and stem cells are discussed to be a potential vehicle for NPs to tumor sites. However, little is known about hazardous effects of NPs in hMSC. The aim of the present study was to analyze functional impairment of hMSC by ZnO- and TiO2-NPs. Cytotoxic effects of NPs were evaluated by the MTT-assay. Furthermore, multi-differentiation capacity, spheroid formation and migration were assessed. The immunophenotype was observed by flow cytometry. Cytotoxic effects were observed at 625 nM ZnO-NPs whereas no cytotoxicity was seen in hMSC by TiO2-NPs. The differentiation capacity of hMSC into osteogenic and adipose lineages was unchanged. A long-term period cultivation of hMSC for 3 weeks after NP exposure revealed a persistence of NPs in the cytoplasm. The migration capability was impaired whereas the ability to form spheroids was not affected. Flow cytometric analysis revealed distinct alteration of cell surface markers CD 90 and CD 73. Major functional properties of hMSC were unaffected by TiO2- and ZnO-NPs. However, restricted migration might critically influence wound healing capacity. Further information is needed to assess the clinical impact of these findings.

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“… In regulation of cell activity, the vesicles from mitochondria were stimulated to act as the primary response to oxidative stress through delivering selected cargo to lysosomes . It has been proved that IRONs could be internalized through vesicles, which transferred the inner content to lysosome to degrade . In terms of cell communication, the vesicles secretion was strongly associated with ion channel between myocytes .…”

Section: Discussionmentioning

confidence: 99%

“…55 It has been proved that IRONs could be internalized through vesicles, which transferred the inner content to lysosome to degrade. 56 In terms of cell communication, the vesicles secretion was strongly associated with ion channel between myocytes. 57,58 The vesicles of cardiac cells in 3D environment due to incubation of DMSA-IRONs might involve in the modulation of cell communication, such as assembly of IDs between cardiac cells.…”

Section: Discussionmentioning

confidence: 99%

Effects of different doses of 2,3‐dimercaptosuccinic acid‐modified Fe₂O₃nanoparticles on intercalated discs in engineered cardiac tissues

Mou

Xiong

et al. 2016

J Biomed Mater Res

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Although iron oxide nanoparticles (IRONs) were applied in clinical magnetic resonance imaging in vivo and magnetic tissue engineering in vitro widely, the underlying effects of IRONs on the development of cardiomyocytes especially the intercellular junctions, intercalated discs (IDs), remain an unknown issue. Given the critical role of threedimensional (3D) engineered cardiac tissues (ECTs) in evaluation of nanoparticles toxicology, it remained necessary to understand the effects of IRONs on IDs assembly of cardiomyocytes in 3D environment. In this study, we first reconstituted collagen/Matrigel based ECTs in vitro and prepared IRONs with 2,3-dimercaptosuccinic acid (DMSA-IRONs). We found that the internalization of DMSA-IRONs by cardiac cells in dose-dependent manner was not associated with the cell distribution in 3D environment by determination of Prussian blue staining and transmission electronic microscopy.Significantly, through determination of western blotting and immunofluorescence of connexin 43, N-cadherin, desmoplakin, and plakoglobin, DMSA-IRONs enhanced the assembly of gap junctions, decreased mechanical junctions (adherens junctions and desmosomes) of cardiac cells but not in dosedependent manner in ECTs at seventh day. In addition, DMSA-IRONs increased the vesicles secretion of cardiac cells in ECTs apparently compared to control groups. Overall, we conclude that the internalization of DMSA-IRONs by cardiac cells in dose-dependent manner enhanced the assembly of electrochemical junctions and decreased the mechanical related microstructures.

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The endocytic penetration mechanism of iron oxide magnetic nanoparticles with positively charged cover: A morphological approach

Cited by 22 publications

References 20 publications

Effects of an 11-nm DMSA-coated iron nanoparticle on the gene expression profile of two human cell lines, THP-1 and HepG2

Effects of an 11-nm DMSA-coated iron nanoparticle on the gene expression profile of two human cell lines, THP-1 and HepG2

Functional Responses of Human Adipose Tissue-Derived Mesenchymal Stem Cells to Metal Oxide Nanoparticles <I>In</I> <I>Vitro</I>

Effects of different doses of 2,3‐dimercaptosuccinic acid‐modified Fe₂O₃nanoparticles on intercalated discs in engineered cardiac tissues

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The endocytic penetration mechanism of iron oxide magnetic nanoparticles with positively charged cover: A morphological approach

Cited by 22 publications

References 20 publications

Effects of an 11-nm DMSA-coated iron nanoparticle on the gene expression profile of two human cell lines, THP-1 and HepG2

Effects of an 11-nm DMSA-coated iron nanoparticle on the gene expression profile of two human cell lines, THP-1 and HepG2

Functional Responses of Human Adipose Tissue-Derived Mesenchymal Stem Cells to Metal Oxide Nanoparticles <I>In</I> <I>Vitro</I>

Effects of different doses of 2,3‐dimercaptosuccinic acid‐modified Fe2O3nanoparticles on intercalated discs in engineered cardiac tissues

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Effects of different doses of 2,3‐dimercaptosuccinic acid‐modified Fe₂O₃nanoparticles on intercalated discs in engineered cardiac tissues