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Table 1 Characterization of cell toxicity according to changes in mRNA expression (transcriptomics), proteome (proteomics), and metabolome (metabolomics) with categories

From: Role of omics techniques in the toxicity testing of nanoparticles

Particle Size (nm) Cell Exp Regulated pathway(s) St Im De Pr Mo Me Ve Si O References
A. Transcriptomics
 Ag 5 L51784 3–6 µg/ml; 4 h Ox. stress, DNA repair X         X [76]
 Ag 5, 100 U937 1–25 µg/ml; 24 h 5 nm: ox. stress, inflammation X X         [80]
 Ag 20 Human dermal fetal fibroblasts 3–6 µg/ml; 4 h Cytoskeleton, energy metabolism, DNA damage      X X    X [122]
 Ag 20, 30, 60 Caco-2, MCF-7 5–25 µg/ml; 6–24 h Proliferation, stress response, ox. stress X    X       [123]
 Ag 20, 50 HepG2 2.5 µg/ml; 4–24 h 20 nm: stress response X          [124]
 Ag 20, 50 Human dermal fibroblasts 200 µM; 1–8 h Cytoskeleton, insulin, HGF signaling, MAPK signaling, ATP content, apoptosis, cytoskeleton    X   X X   X X [52]
 Ag 20, 50 A549 1–3 µg/ml; 24–48 h Cell cycle, ox. stress X    X       [65]
 Ag 20, 50 HepG2 1–3 µg/ml; 24–48 h Cell cycle progression (low dose), morphological damage (high dose)     X       [75]
 Ag < 100 HeLa 20 µg/ml; 24–48 h Metabolic process, cellular process, stress response, apoptosis, cell cycle X   X X      X [125]
 Ag 100 Embryonic rat cells 20 µg/ml; 48 h Energy, metabolism, O2 transport, inflammation, molecular binding   X     X    X [69]
 Al2O3 < 100 A549 100 µg/ml; 0–72 h Cell death, cell cycle arrest    X X       [81]
 Au (NH2, COOH, OH) 17–22 Human mesenchymal stem cells 50 µg/ml; 4 h TFG-β, FGF-2          X [126]
 Au 5, 30 Caco-2 200–300 µM; 24–72 h Ox. stress, apoptosis, growth inhibition X   X X       [127]
 Au 20, 34, 61, 113 Caco-2/M-cells 0.5–64 µg/ml; 10–21 days Ox. stress, ER stress, apoptosis X   X        [128]
Particle Size (nm) Cell Tech Regulated pathway(s) St Im De Pr Mo Me Ve Si O References
A. Transcriptomics
 CdSe/ZnS 8–10 HSF-42 8–80 nM; 48 h Carbohydrate binding, intracellular vesicle formation, stress response, mitosis, cytokinesis X    X    X   X [66]
 CeO2 3 Caco-2 170 µg/ml; 24–72 h Mitochondrial function       X     [129]
 CuO 50 A549 25 µg/ml; 24 h Mitosis, cell death, p38 pathway    X X     X   [130]
 CuO (rods, spherical) 12, 50–80 Caco-2 5–100 µg/ml; 24–120 h Inflammation, ox. stress (rod > spherical) X X         [111]
 Fe3O4 (COOH, NH2, bare) 14–18 HCM, BE-2-C, 293T 20–80 µg/ml; 2 days Ox. stress, proliferation X    X       [131]
 Fe3O4 32 RAW264.7, Hepa1–6 30–100 µg/ml; 4–48 h Immune effects, cell death, homeostatic processes   X X    X     [132]
 Fe3O4 32 THP-1, HepG2 50–100 µg/ml; 24 h Various pathways; HepG2: cell growth, mobility, metabolism     X X X     [104]
 Fe2O3, SiO2, TiO2, ZnO 3, 10, 5, 8–10 RKO, Caco-2, HaCaT, SKMel28 10, 5–50, 1–5 µg/cm2; 4 h Ox. stress response all lines, ZnO in addition protein folding X         X [99]
 Fe2O3, SiO2, ZnO 100 HEK293 100, 12.5 µg/ml; 24 h Inflammation, stress, cell death X X X        [107]
 MWCNT 5–10 × 20–30 Caco-2, diff. THP-1, small airway cells 10–100 µg/ml; 24 h Apoptosis, inflammation, cell adhesion   X X   X      [93]
 PEG-silane qdots 10–13 IMR-90 8–80 mM; 48 h Mitosis, spindle formation     X X      [66]
 SiO2 10, 500 RAW264.7 5–50, 250–1000 µg/ml; 24 h Transcription, cell cycle progression, inflammation response, apoptosis, morphogenesis, differentiation   X X X      X [54]
 SiO2 12 A549 0.1–6 µg/ml; 24–72 h Ox. stress response; membrane trafficking; inflammatory response X X      X    [78]
 SiO2 12, 5–10, 10–15 FE1 cells 12.5–100 µg/ml; 24 h Lysosomal genes        X    [74]
 SiO2 14, 20 A549 0.05–0.6 mg/ml; 2 h Inflammation, apoptosis, matrix metalloproteinases   X X       X [133]
 SiO2 67 A549, CCD-34Lu, H2347 0.1–1.5 mg/ml; 24–48 h Inflammation, signal transduction, cell death regulation   X X      X   [82]
 SWCNT 1–2 × 1000–2000 EAhy926 50 µg/ml; 24 h Inflammation, ox. stress, and apoptosis X X X        [53]
 TiO2 anatase 7, 20, 200 HaCaT n/a; 2–24 h Inflammation response, cell adhesion   X    X      [55]
 TiO2, ZnO 12, 15 Jurkat, prim macrophages, DCs 1–10 µg/ml; 6–24 h Ox. stress related all cell lines, cell death, cell growth, immune system; TiO2 inert X X X X       [94]
 TiO2 7000 × 200 × 10 Caco-2, diff. THP-1, small airway cells 10–100 µg/ml; 24 h Apoptosis, cell cycle, inflammation, cell adhesion, phagocytosis   X X X X     X [93]
 WC, WCCo 56, 62 HaCaT 30; 3 µg/ml; 3 h–3 days Hypoxia-related response, carbohydrate metabolism, endocrine pathways       X    X [106]
 ZnO 20 HaCaT 10–80 µg/ml; 24 h Apoptosis, ox. stress X   X        [56]
 ZnO 20, 60 A549 25 µg/ml; 24 h DNA damage, apoptosis, ox. stress X   X       X [134]
 ZnO 28 × 96, 36 × 95, 44 × 73, 25 Olfactory cells, human stellate cells 2.5–10 µg/ml; 24 h Stress response, inflammatory response; stress, cell growth and survival, cell signaling X X X X     X   [135, 136]
A. MiRNomics
 Ag 20 Human neural stem cells 10–200 µg/ml; 6–24 h Cell cycle arrest, apoptosis, ox. stress, dysfunctional neurogenesis X   X X      X [57]
 Ag 30 Jurkat 0.2 µg/ml; 24 h DNA damage, apoptosis, ox. stress X   X        [137]
 Fe2O3 3–7 PC-12 214 µg/ml; 24 h Apoptosis, phagocytosis, inflammation, metabolism, endocytosis   X     X X   X [138]
 MWCNT 100 × 13,000 BEAS-2B 0.25–2 µg/cm2; 1–48 h Mitochondria, gluconeogenesis, microtubuli function      X X     [139]
B. Proteomics
 Au 2.2, 5.9, 17 K562 cells 10 mM; 3–24 h ER stress X          [79]
 Au 5, 15 Balb/3T3 58.8 µg/ml; 72 h Cell growth, proliferation, morphology, cell cycle, ox. stress, inflammation, ECM synthesis X X   X      X [71]
 Ag 20, 200 Caco-2/TC7:HT29-MTX 1 µg/ml; 24 h Cytoskeleton rearrangement, cell cycle, ox. stress, metabolism X    X X X     [58]
 Au 20 Dermal fibroblasts 200 µM; 1–8 h Signal transduction, cytoskeleton, energy metabolism, ox. stress X     X X   X   [140]
 Au 20 Small airway cells/MRC-5 1 nM; 72 h Cell adhesion      X      [70]
 NH2-Au, CuO, NH2-CdTe 20 THP-1 15, 22, 5 µg/ml; 48 h Topoisomerase (CdTe), ox. stress (CuO), NfkB (Au) X        X X [108]
 Au 5, 30 Caco-2 59 µg/ml; 72 h Metabolism, Energy, transcription, protein, cell morphology and transport, signal transduction, growth, proliferation, antioxidant activity, apoptosis, cell adhesion, cytoskeleton orientation X   X X X X    X [59]
 Au 20 MRC-5 1 nM; 72 h Ox. stress, cytoskeleton, cell cycle regulation, DNA repair X    X X     X [141]
 Au 20, 100 LoVo 10 µg/ml; 24 h 100 nm: PAK, MAPK, phosphatase 2A pathway; 20 nm: cell stress, protein carbonylation X        X   [60]
 CoO, Fe3O4, SiO2 < 100, 13, 15 RAW264.7 6.25–25 µg/ml; 24 h ER stress, phagocytosis X         X [101]
 CuO 30–50 BEAS-2B 0.01 µg/cm2; 24–72 h Maintenance, protein synthesis, death/survival, cell cycle, morphology    X X   X    X [72]
 Cu, CuO 250 RAW264.7 5–10 µg/ml; 24 h Ox. stress response, GSH synthesis, cytoskeleton, mitochondrial proteins X    X   X     [61]
 CuO, TiO2 22, 25 Murine macrophages 5–10, 100 µg/ml; 24 h Ox. stress response X          [77]
 Fe3O4 10, 100 NRK-52E 1 ng/well; 24 h Cell death related, ras-related, GSH-related, HSP, serpin H1, ER-resident proteins X   X       X [142]
 MWCNT (0.6 × 3.6) * 10E3 HEK 0.4 mg/ml; 24–48 h Metabolism, cell signaling, cell stress, vesicular trafficking, cytoskeleton X     X   X X   [143]
 MWCNT (0.1 × 10–20) * 10E3 U937 30 µg/ml; 24 h Metabolism, biosynthesis, stress response, differentiation X      X    X [144]
 MWCNT 30 × < 1000 A549 0.3–300 µg/ml, 2–24 h Proliferation, ox. stress, cytoskeleton X    X X      [62]
 SiO2 25 A549 100 µg/ml; 24 h Apoptosis, cytoskeleton, ox. stress response, protein synthesis X   X   X X     [67]
 SiO2 15, 30 HaCaT 10 µg/ml; 24 h Metabolism, ox. stress, cytoskeleton, molecular chaperones, apoptosis X   X   X X    X [68]
 SWCNT 1–6 × 1000–2000 HepG2 0.1–100 µg/ml; 24 h Redox regulation, signaling, cytoskeleton formation, cell growth X    X X    X   [145]
 SWCNT, (plain, PEGylated) (0.7–1.6 × 0.2–3) * 10E3 PC-12 0.1–100 µg/ml; 24 h Antioxidant reactivity, nucleic acid metabolism, lipid metabolism, mitochondrial function X      X    X [63]
 TiO2 18–80 BEAS-2B 10 µg/ml; 24 h Stress response, metabolism, adhesion, cytoskeleton dynamics, cell growth, cell death, cell signaling X   X X X X   X X [146]
 TiO2, (coated, plain) 20 Human and rat macrophages 300; 24 h//20 µg/ml; 8–48 h Metabolic homeostasis, cytoskeleton remodeling, ox. Stress X     X X     [73, 147]
 TiO2 24 A549 2.5–50 µg/ml; 2 month Glucose metabolism, mitochondrial function, proteasome activity, DNA damage response, p53 activation, cell cycle, proliferation     X   X    X [148]
 ZnO, ZrO 40 J774 10 µg/ml; 24 h Mitochondrial function, phagocytosis, DNA damage      X     X [100]
 ZnO (Al-doped) 20–40 A549 20–500 µg/ml; 2–48 h p53 activation, extracellular signaling         X   [149]
C. Metabolomics
 Ag 10, 30, 69 HaCaT 10–100 µg/ml; 24 h Glycolysis, energy production       X     [150]
 Al2O3 64 Human bronchial epithelial cells 50–500 µg/ml; 24 h Apoptosis, ox. stress, mitochondrial function X   X    X     [151]
 Au 2 SH-SY5Y 100 ng/ml; 2–6 h Ox. stress, immune response X X         [83]
 CuO 28 A549 5–40 µg/ml; 4–24 h Ox. stress, hypertonic stress, apoptosis X   X       X [64]
 CuO < 50 Murine bone marrow MSCs 2–100 µg/ml; 48 h Serine, glyceric acid, and succinic acid, glutamine       X     [32]
 TiO2 5 L929 100 µg/ml; 48 h Amino acid level changes       X     [152]
 TiO2 < 100 L929 100 µg/ml; 48 h Carbohydrate metabolism, energy metabolism, mitochondria       X     [153]
  1. Exposure (Exp) with concentration and collection time after treatment with nanoparticles is given. If a range is indicated, several concentrations or time points have been evaluated