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

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]

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

Caco-2

170 µg/ml; 24–72 h

Mitochondrial function

X

[129]

 CuO

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

RAW264.7, Hepa1–6

30–100 µg/ml; 4–48 h

Immune effects, cell death, homeostatic processes

X

X

X

[132]

 Fe₃O₄

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

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

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

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

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

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

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

Dermal fibroblasts

200 µM; 1–8 h

Signal transduction, cytoskeleton, energy metabolism, ox. stress

X

X

X

X

[140]

 Au

Small airway cells/MRC-5

1 nM; 72 h

Cell adhesion

X

[70]

 NH₂-Au, CuO, NH₂-CdTe

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

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]