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Table 1 Toxic effects and mechanisms of CuONPs  

From: PINK1/TAX1BP1-directed mitophagy attenuates vascular endothelial injury induced by copper oxide nanoparticles

Nanoparticle source

Particle size

Dose

Exposure time

Cell line/in vivo models

Mechanism of toxicity

References (DOI)

Sigma-Aldrich

 < 50 nm

100 mg/kg body weight (intraperitoneal instillation)

14 d

Wistar male rats

Oxidative stress, DNA damage and apoptosis in liver

10.1038/s41598-020-67784-y

Self-synthesized

 

0, 1.25, 2.5, 5, 10 and 20 μg/ml

48, 72 h

Renal cell carcinoma (786O, A498, CAKI-1, SR786O and HK-2)

ER stress; Apoptosis

10.1016/j.biomaterials.2017.09.008

Sigma-Aldrich

 < 50 nm

0–80 μg/ml

4, 24 h

Rat small intestine epithelial cells (IEC-6)

3D human small intestinal tissue model (EpiIntestinal)

ROS production; Cytotoxicity

10.1080/17435390.2019.1578428

Sigma-Aldrich

20–40 nm

10 μg/g body weight (intranasal perfusion)

60 d

Rat liver cells (BRL 3A); Wistar male rats

Oxidative stress, ER stress and apoptosis in liver

10.1016/j.jhazmat.2020.123349

Self-synthesized

141 ± 13 nm in water

0, 10, 100, 1000 μM

5 h

Rat glioma cell line (C6)

ROS production; Cytotoxicity

10.1007/s11064-016-2020-z

Self-synthesized

75 nm

0, 1.25, 2.5 and 5 μg/ml

24 h

Primary human umbilical vein endothelial cells (HUVECs)

Impairment of  angiogenesis

10.1039/c3nr04363k

Sigma-Aldrich

 < 50 nm

0, 5, 10, 15 and 20 μg/ml

12 h

Murine macrophage J774A.1

Lysosomal damage; Oxidative stress; Inflammation

10.1016/j.jhazmat.2021.125134

Self-synthesized

 

15.63–625 μM

24 h

Mouse fibroblasts (L929)

DNA damage; ROS production

10.1016/j.tiv.2021.105252

Sigma-Aldrich

 < 50 nm

1.25, 2.5 or 5 mg/kg (intratracheal instillation)

3 d

Male C57BL/6 mice

Oxidatives stress; Autophagy dysfunction; Acute lung injury

10.1186/s12951-021-00909-1

Ionic Liquides Technologies

15–100 nm

0–240 μg/ml

18 h

Leukemic cell line (HL60)

Mitochondrial damage; ROS production; DNA damage

10.1016/j.tiv.2015.05.020

Sigma-Aldrich

 < 50 nm

0, 10, 20, and 40 μg/ml

0, 1, 3, 6, 12 h

Human umbilical vein endothelial cells (HUVECs)

Lysosomal impairment; ROS production; DNA damage

10.2147/IJN.S241157

10.1016/j.lfs.2020.117571

10.1016/j.freeradbiomed.2018.09.032

10.1016/j.biomaterials.2018.01.048

Sigma-Aldrich

 < 50 nm

0, 5, 10, 15, 20 μg/ml (in vitro);

2.5–5.0 mg/kg (intratracheal instillation)

12 h

3 d

Human umbilical vein endothelial cell line (EA.hy926);

Male C57BL/6 mice

Mitochondrial dysfunctions; mtROS production; Vascular injury

This study

Sigma-Aldrich

 

0, 0.01, 0.1, 1, 10, 100 μM

48 h

Human SH-SY5Y neuroblastoma cells (CRL-2266)

Human neuroglioma H4 (HTB-148)

Rat PC12 (CRL-1721)

ROS production; Apoptosis

10.3390/ijerph17031005

Self-synthesized

124 nm

10 μg/ml

24 h

Human pancreatic cancer cell line (PANC1)

Mitochondrial dysfunctions; ROS production; Apoptosis

10.1038/s41598-019-48959-8

Sigma-Aldrich

 < 50 nm

0, 1, 5, 10 and 20 μg/ml

24 h

Human alveolar epithelial cell line (A549)

Human cervix carcinoma cell line (HeLa S3)

Cytotoxicity and genotoxicity

10.1186/1743-8977-11-10

Sigma-Aldrich

 < 50 nm

30 μg/ml

24 h

Human alveolar epithelial cell line (A549)

Autophagic cell death

10.1371/journal.pone.0043442

Sigma-Aldrich

50 nm

25 μg/ml

24 h

Human alveolar epithelial cell line (A549)

ROS production; Cytotoxicity

10.1021/nn202966t

Self-synthesized

  

36 h

Human alveolar epithelial cell line (A549)

Inflammation and apoptosis

10.1007/s10529-017-2463-6

Sigma-Aldrich

 < 50 nm

0, 2, 4, 6, 8 and 10 μg/ml

24 h

Human colorectal adenocarcinoma cell line (HT29)

Cytotoxicity

10.1007/s00204-017-1976-z

Self-synthesized

30 ± 3.5 nm

0, 4, 6 and 12 μg/ml

24 h

Human breast cancer cells (MCF7)

Apoptosis; Protective autophagy activation

10.1016/j.bbagen.2013.08.011

Sigma-Aldrich

 < 50 nm

1, 2, 5, 10, 20, and 40 μg/ml

24 h

Human airway epithelial cells (HEp-2)

Oxidative damage; ROS generation; Apoptosis

10.1007/s12011-022-03107-8

Nanostructured & Amorphous Materials Inc

50 nm

2.5–5.0 mg/kg (intratracheal instillation)

0, 1, 3, 7 d

Female C57BL/6 mice

Protein chlorination and acute lung inflammation

10.3390/ijms22179477

Sigma-Aldrich

 < 50 nm

0, 25, 50, and 100 μg/kg (intratracheal instillation)

48 h

Female BALB/c mice

Human airway epithelial cell line (NCI-H292)

Inflammatory responses and collagen deposition in lung tissue

10.1080/17435390.2018.1432778

Sigma-Aldrich

46.5 nm

1, 2.5, 5, and 10 mg/kg body weight (nasal instillation)

7, 14 and 28 d

C57BL/6 mice

Alveolar and bronchial epithelial cell lines (A549 and BEAS-2B)

Pulmonary infammation and fibrosis in mice

Cytotoxicity and apoptosis in epithelial cells

10.1038/s41598-018-22556-7

Self-synthesized

40 nm to 110 nm

0, 0.625, 1.25, 2.5 and 5 μg/ml

48 h

Bladder cancer cell lines (T24, J82, 5637, and UMUC3)

ROS production; Cell cycle; Apoptosis

10.1038/cddis.2013.314

Intrinsiq Materials Ltd

28.2 ± 13.7 nm

10 μg/ml

0, 1, 3, 6, 12, 24, 48 h

Alveolar epithelial cell line (A549)

Oxidative stress; Apoptosis

10.1186/s12989-016-0160-6

Self-synthesized

4, 24 nm

0, 0.5, 1.0, 1.5 and 2.0 mM

0, 1, 4, 24, 48 h

Alveolar epithelial cell line (A549)

ROS production; Cytotoxicity

10.1039/c5en00271k

Sigma-Aldrich

20–40 nm

0, 1, 5 and 10 μg/ml

4 h

Alveolar and bronchial epithelial cell lines (A549 and BEAS-2B)

DNA damage; Cytotoxicity

10.1002/smll.201201069