Table 1.
Toxic effects of ZnO nanostructures to normal mammalian cells and cancer cells.
| Shape & Size | Cell Type | ZnO Dose & Exposure Time | Cytotoxic Effect | Ref. |
|---|---|---|---|---|
| Normal cells | ||||
| Polygonal nanoparticles (NPs); 55 nm | Human HaCaT cells & gingival fibroblasts | 10, 15, 30 and 100 µg/mL for 24 h | No toxicity up to 15 µg/mL ZnO NPs. Viability < 50% at a dose of 100 µg/mL |
[135] |
| Tetrapods (length: 500 nm–50µm; thickness: 200 nm–2µm); Spherical NPs (150 nm) | Human dermal fibroblasts | 15.2, 25.3 and 35.5 µg/mL for 24 h | Tetrapods are relatively less toxic than ZnO NPs that release more Zn2+ ions. The minimal size of tetrapods and diameter of NPs fall in sub-micrometer scale. | [53] |
| Spherical NPs; 22 nm | Human HaCaT cells | 10, 20, 40 and 80 μg/mL for 24 h. | Dose-dependent toxicity. Mitochondrial dysfunction, lactase dehydrogenase (LDH) leakage, and reactive oxygen species (ROS) generation | [136] |
| Nanorods; 47.8–52.5 nm | Human erythrocytes | 50, 100, 250 and 500 ppm for 1 h at 37 °C | Lipid peroxidation of cell membrane, causing hemolysis; ROS generation | [140] |
| Polygonal NPs; 60 nm | Murine retinal ganglion cells | 0.63, 1.25, 2.5, 5, & 10 µg/mL for 24, 48, 72 h | Dose-dependent toxicity. Excessive ROS creation leads to overexpression of caspase-12 and final cell death | [123] |
| Commercial NPs | Murine GC-1 spg cells | 1, 2 and 4 µg/mL | Dose-dependent toxicity. Induced autophagy due to elevated microtubule-associated proteins 1A/1B light chain 3-II (LC3-II) & Beclin1 levels. Elevated levels of BcL2-associated X protein (Bax), caspase 3 and caspase 8 |
[49] |
| Spherical NPs; 20–110 nm | Murine Leydig & Sertoli cells | 5, 10, 15 and 20 µg/mL for 12 h and 24 h | Internalization of ZnO NPs. Dose- and time-dependent toxicity. Apoptosis at doses ≥ 15 µg/mL due to LDH & ROS | [143] |
| Nanorods (width: 15.38 nm; length: 82.34 nm) | Murine JB6 Cl 41-5a skin cells | 5, 10 and 20 µg/mL for 24, 48 and 72 h | Mitochondria dysfunction, dose-and time-dependent ROS generation | [137] |
| Nanorods (width: 40 & 80 nm; length: 80–250 nm); NPs (20 nm) | Murine L929 fibroblasts | 0.1, 0.2, 1, 3, 5 & 7 mM for 24, 48 and 72 h | Size- and dose-dependent toxicity. Shape changes from elongated to rounded forms at a ZnO dose of 5 mM | [144] |
| Nanorods; 45 nm | Primary rat astrocytes | 4, 8 and 12 µg/mL for 6, 12 and 24 h | Reduce cell viability, increase LDH and ROS levels, activate caspase 3 in a dose- and time-dependent manner | [139] |
| Cancer cells | ||||
| Polygonal NPs; 30 nm | HepG2 | 0.8, 2, 8, 14 and 20 µg/mL for 6 h, 12 h & 24 h | Dose- and time dependent toxicity. Cell viability decreases while LDH rises at doses ≥14 mg/mL for 12 h & 24 h Induce ROS, so reducing mitochondrial membrane potential (MMP), and activating Bax, Bcl2, p53 & caspase 9 | [50] |
| Polygonal NPs; 21.34 nm | HepG2, A549 & primary rat cells | 5, 10 & 15 µg/mL for 24 h | Selective killing to HepG2, A549 by inducing dose-dependent cytotoxicity. Upregulation of Bax and p53 gene levels, and downregulation of Bcl2 | [148] |
| Spherical NPs; 13 nm | MCF-7 & HepG2 | 2.5, 5, 10, 25, 50 & 100 µg/mL for 24 and 48 h | Dose-and time-dependent toxicity. Apoptosis due to ROS production, upregulation of Bax, p53 & caspase 3 | [150] |
| Polygonal; 10–59 nm | MCF-7 | 62.5, 125, 250, 500, and 1000 µg/mL for 24 h | ZnO NPs arrested the cell cycle in the G2/M phase. Upregulation of p53, p21, & Bax, and downregulation of Bcl2, and extracellular regulated kinases (ERK1/2) in a dose-dependent manner | [152] |
| Spherical NPs; 15–18 nm | A549 | 0.1, 10 and 100 µg/mL for 4, 24 and 48 h | Uptake of extracellular Zn2+ ions induce ROS and deoxyribonucleic acid (DNA) damage | [122] |
| Spherical NPs; 30, 80 & 200 nm | THP-1 monocytes & macrophages | 1, 10, 25, 50, 75, and 100 µg/mL | Size- and dose-dependent toxicity. Intracellular dissolution of NPs yield Zn2+ ions & mitochondrial superoxide | [126] |
| Spherical NPs; 25–40 nm | HEK293 | 5, 15, 25, 50, 75 and 100 µg/mL for 3, 24 & 48 h | Dose-and time-dependent toxicity. Generation of ROS and oxidative stress, causing MMP reduction, loss of lysosomal activity, and apoptosis | [147] |
| Polygonal NPs; 20 nm | SKOV3 | 5, 10, 20 and 30 μg/mL for 12 h & 24 h | Dose- and time-dependent toxicity. Apoptosis at doses ≥20 μg/mL through the ROS creation, MMP reduction, upregulation of p53, Bax, caspase 9, & downregulation of Bcl2 | [156] |
| Polygonal NPs; 55 nm | Ca9-22 | 10, 15, 30 and 100 μg/mL for 24 h | Apoptosis at doses ≥30μg/mL due to ROS creation, MMP reduction and DNA fragmentation | [135] |
| Hexagonal prismatic NPs; 18.5 and 47.1 nm | SHSY5Y | 5, 10, 20, 40, 60, 80 & 100 µg/mL for 2, 6, 12 and 24 h | Size- and time-dependent toxicity. Intracellular Zn2+ ions induced the generation of ROS and oxidative stress, leading to mitochondria dysfunction, cytoskeletal disruption, and apoptosis | [154] |
| Spherical QDs; 7.10 nm | HEK 293T & HeLa | 25, 50,100, 200 & 400 µg/mL for 6, 24, 48 and 72 h | Dose- and time-dependent cytotoxicity. ROS production in both cell types in a time- and dose-dependent manner, causing MMP reduction | [162] |
| Nanorods (width: 40 & 80 nm; length: 80–250 nm); NPs (20 nm) | HeLa | 0.05, 0.1, 0.2, 1, 2, 3,4 & 5 mM for 24, 48 and 72 h | Size- and dose-dependent toxicity. ROS generation and released Zn2+ ions are responsible for apoptosis | [144] |