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Table 4 Results of estimation of nanoparticle toxicity in experimental models of their transdermal uptake

From: Dependence of Nanoparticle Toxicity on Their Physical and Chemical Properties

Type of nanoparticles

Sizes

Concentration; incubation time

Cell line

Method of detection

Effects; conclusions

Reference

Ag NPs modified with digallic acid (DA-Ag) and not modified

DA–Ag, 13, 33, and 46 nm;Ag, 10–65 nm

1–10 μg/ml; 24 h

291.03C

RAW 264.7

Neutral red assay; flow cytometry; TEM; [3H]thymidine staining of DNA; estimation of mitochondrion activity (JC-1 test)

The Ag NPs decrease the proliferation rate of both cell lines. The NPs enhance ROS generation in RAW 264.7 cells. RAW 264.7 cells absorb the 10- to 65-nm Ag and 33 and 46-nm, DA-Ag NPs, whereas 291.03C cells absorb only the 13-nm DA–Ag NPs. The Ag NPs suppress the production of TNFα by RAW 264.7 cells and enhance its production by 291.03C cells. The 33- and 46-nm DA-Ag NPs are the least toxic.

[163]

Si NPs modified with Al2O3 (Al2O3-Si) and Na (Na-Si)

Al2O3-Si, 21 nm; Na-Si, 30 nm

40–800 μg/ml; 72 h; 7 days

3T3-L1

WI-38

WST-1; LDH assay; glutathione level measurement

The Al2O3-Si NPs are nontoxic for 3T3-L1 cells and slightly toxic for WI-38 cells (a small decrease in viability at an NP concentration of 250 μg/ml). The Na-Si NPs are toxic for both 3 T3-L1 and WI-38 cells.

[164]

ZnO NPs modified with NH2 groups

20 nm

1–50 μg/ml; 0.5–24 h

HaCaT

SCCE02

MTT assay; immunoblotting; ELISA; TEM; real-time PCR; ROS assay; fluorescent microscopy

Decreased viability of both cell lines at NP concentrations of 10 μg/ml and higher. Induction of oxidative stress through activation of MAP kinase signal pathways (ERK, JNК, and p38). Enhanced expression of Egr-1 and, as a consequence, TNFα.

[165]

Multiwalled carbon nanotubes (MWCNTs)

Diameter, 12 nm

100 μg/ml

SZ95

IHK

MTS assay; LDH assay; transepithelial electrical resistance measurement; [3H]thymidine staining of DNA; TEM

MWCNTs are toxic only for IHK cells.

The TEER is unchanged, which indicates that MWCNTs do not affect the tight junctions of epidermal cells.

[166]

ZnO and TiO2 NPs

268.1 ± 11.2 and 414.9 ± 4.5 nm

0.5–10 μg/ml; 24, 48, and 72 h; 3 months

NCTC2544

MTS assay; scanning electron microscopy; ROS assay; flow cytometry

Decrease in viability upon incubation in the presence of the ZnO NPs at concentrations higher than 15 μg/ml for 24–72 h. Prolonged incubation causes changes in cell morphology and affects the cell cycle.

The TiO2 NPs are nontoxic.

The NP toxicity is related to the release of metal ions inducing oxidative stress.

[167]

CdSe/CdS NPs modified with polyethylene glycol

39–40 nm

0.3125–10 nM; 24 and 48 h

NHEK

Confocal microscopy; TEM; flow cytometry; atomic emission spectroscopy

Decreased viability at NP concentrations higher than 1.25 nM. Enhanced IL-8 and IL-6 production.

[168]

NaYF4 NPs modified with different compounds

94–550 nm

62.5 and 125 μg/ml; 24 h

HaCaT

Human skin fibroblasts

MTT assay; confocal microscopy; fluorescent microscopy

The NPs coated with polyethyleneimine (PEI), poly(lactide-co glycolide) (PLG), and PLG + dextran sulfate are the most toxic (52, 61, and 72% viable cells, respectively).

The NPs are nontoxic for fibroblasts. Hydrophilic NPs are the least toxic and are the most readily absorbed by the cells.

[169]

TiO2 NPs

124.9 nm

0.008–80 μg/ml; 6, 24, and 48 h

A431

MTT assay; Bradford protein assay; flow cytometry; glutathione level measurement; lipid peroxidase assay; DNA comet assay; ROS assay

A slight decrease in cell viability after 48 h of treatment.

DNA damage with ROSs and micronucleus formation.

[170]

Polyamidoamine (PAMAM) dendrimers

4.5, 5.4, and 6.7 nm

0.01–21 μM;

24 h; 8 days

HaCaT

SW480

MTT, clonogenic, Alamar Blue, and neutral red assays

The toxicity of the dendrimers linearly increases with increasing both their zeta potential and their size.

[171]

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