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Table 4 Size-dependent cytotoxicity of NPs

From: Engineered nanoparticles interacting with cells: size matters

NPs

Size (nm, Ø)

Cell lines

Evaluation techniques

Main conclusions

Ref

Au

0.8–15

SK-MEL-28, HeLa, L929, J774A1

TEM, MTT assays, FACS

Cytotoxicity depends on size, not ligand chemistry; small NPs more toxic

[89]

QDs

2.2, 5.2

PC12, N9

MTT assays

Smaller NPs more toxic

[72]

Au

5, 15

Balb/3 T3

Colony forming efficiency, Trypan Blue assays

5 nm, toxic; 15 nm, non-toxic

[95]

Au

3–38

J774 A1

Sizing and counting of cells

AuNPs, increased toxicity for larger NPs; AgNPs, no size-dependence in toxicity

[93]

Ag

3–25

Au

10–25

HDMEC, A549, NCIH441

MTS assays, Ki-67 expression, LDH release

Size not a significant factor for cytotoxicity compared with surface ligands

[96]

Ag

15–55

F-12 K

MTT assays, LDH leakage, ROS production, MMP, inflammatory response

Increased toxicity for smaller NPs

[97]

Ag

4–70

U937

Cell viability, ROS production, cytokine release assays

Size-dependent toxicity (4 nm highest)

[90]

SiO2

32, 83

Caco-2

WST-1 assays, comet assays

No cytotoxicity detected for either size

[55]

polymer

45, 90

NR8383, Caco-2

Mitochondrial membrane potential, ROS production, ATP depletion, TNF-α release

Positively charged 45-nm NPs more toxic than equally charged 90-nm NPs

[92]

Ag

10–100

MC3T3, PC12

Cell viability, ROS production, LDH release assays, gene expression, apoptosis detection

10 nm: greatest amount of apoptosis

[98]

TiO2

14–196

osteoblasts, L-02, HEK 293

Alkaline phosphatase and zymography evaluation

Size-dependent cytotoxicity, 100 nm critical size

[99]

Au

20, 200

DU-145

MTS assays

Both sizes cytotoxic

[100]

SiO2

50, 200

GT1-7

Counting cells, intracellular calcium homeostasis

200 nm: no toxic effects, 50 nm: toxicity with Ca level increase

[91]

  1. Abbreviations used: MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, FACS fluorescence-activated cell sorting, LDH lactate dehydrogenase, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) tetrazolium, ROS Reactive Oxygen Species, MMP mitochondrial membrane potential, WST water-soluble tetrazolium salt.