Table 1.
Toxic effects and mechanisms of CuONPs
| 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 |