Table 1.
Cytotoxic effect of AgNPs in different lung cell lines.
| Coating | Size (nm) | Concentration (μg/mL) | IC50
(μg/mL) a |
Exposure Time (h) | Cell Line | Outcomes | Cytotoxic Response | Ref |
|---|---|---|---|---|---|---|---|---|
| Monocultures | ||||||||
| PVP | 20 | 0, 10, 25, 50, 100 and 200 | 100 | 24, 48, 72 | A549 | Gene and protein expression decreases of p53, p21, MDM,2, and caspase 3. Mitochondrial ROS production. Global acetylation levels decrease on tails of histone H3 protein. Global DNA methylation increases. Late apoptosis/necrosis increase after 48 h. HMOX1 has a high expression on A5 and 49, might it render them less susceptible to ROS-induced cell death early-stage apoptosis. |
Concentration-, and Time-dependency. | [41] |
| PVP | 10, 20 | 5–10 | 10 nm: 56.4 20 nm: >100 |
24, 48 | A549 | Severe ADN damage. Cell cycle arrest, increase in several of cells at S and sub-G1 phases (DNA repair mechanism more effective on 10 nm AgNPs). A decrease in cell viability. Increase of late-apoptotic and necrotic cells at 100 μg/mL. |
Size-, Concentration-, and Time-dependency. | [42] |
| PVP | 23 | 1–10 | NS | 24, 48, 72 | A549 Calu-1 BEAS-2B NCI-H358 |
Cell cycle arrest. Cell viability decreased in all cell lines except NCI-H358. Mitochondrial ROS production and protein oxidation, particularly on AgNPs sensitive cell lines. Decrease in cellular ATP levels. Cell arrest on G2 and S-phase for A549 and Calu-1 and S-phase for BEAS-2B. NCI-H358 cells did not show cell cycle changes related to AgNPs exposure. |
Concentration-, Time-, and Cell type dependency. | [43] |
| PVP | 25 | 0.4, 1, 4, 10 | >100 | 240 | NHLF MRC-5 |
Moderate acute toxicity for MRC-5 and cellular senescence using sub-toxic concentrations associated with β-galactosidase (SA-β-gal) activity and heterochromatin foci (SAHF) Expression of SASP and inflammatory genes G2/M phase arrest completed after 10 days 685 transcripts upregulated and 718 transcripts downregulated in RNA-seq global mRNA levels Potential role of the COX2-PGE2 pathway in AgNPs-induced lung cellular senescence. COX2-PGE2 pathway regulated by p65 and highly differentiated. BCL-2 downregulated by AgNPs subsequently undergoes apoptosis. |
Concentration-, and Cell type-dependent. | [44] |
| PVP | 50 and 200 | 5.6, 11.5, 22.5, 45 | NR | 16 | NR8383 | Increase of lactate deshydrogenase (LDH) and glucuronidase (GLU) activity. TNH-α increase at lower concentration of 50 nm citrate-AgNP and at the higher concentration of PVP-AgNP | Concentration-dependent | [40] |
| Shikonin | 20 | 0.078–10 | 2.4 ± 0.11 | 24 | A549 | Cell viability and proliferation decrease. | Concentration-, and | [45] |
| Acacia nilotica, NG, or TKP | 10–78 | 10–100 | Wi38: 86.15 A549: 65.85 |
12, 24, 48 | A549 Wi38 |
Cytotoxic selective to cancer cells. Inhibition of cell cycle. ROS mediated apoptosis. |
Cell-type-dependent. | [46] |
| Gallic acid | 10–30 | 5, 25, 50, 100, 200 | 46.5 | 24 | A549 | Effective in treating the radiation toxicity and resistance developed by the cancer cells during cancer treatment. Cell viability decrease. Epithelial-Mesenchymal Transition suppression. |
Concentration-dependent. | [47] |
| Caulerpa taxifolia | 10–100 | 10–100 | 40,000 | 24 | A549 | Morphological damage and condensation morphology. Cell death. Apoptosis/necrosis induction. |
Concentration-dependent. | [48] |
| Avicennia marina | 10–20 | 10–80 | 50,000 | 24 | A549 | Cancer cell growth inhibition. Damage to the mitochondrial membrane. ROS. |
Concentration-dependent. | [49] |
| Tinospora cordifolia | 25–50 | 25, 50, 75, 100, 150 | 100 | 12, 24, and 48 | A549 | Cell viability decrease. Cytomorphological changes. Apoptosis. Nuclear damage. ROS. Loss of mitochondrial membrane potential (ψm). |
Concentration-, and Time-dependent. | [50] |
| Wogonin | 5, 40 | 2–10 μM 1–5 μM (Ag content) |
5 nm: 2 μM 40 nm: 6 μM |
24 and 48 | A549 | Cell viability decrease. ROS. Activation of the mitochondrial apoptotic pathway. DNA damage. Activation of Caspase-9 and Caspase-3. Secretion of pro-inflammatory markers such as TNFα. |
Concentration-, and size-dependent. | [51] |
| Artemisia oliveriana | 10.63 | 5, 25, 50, 100 and 200 | A549: 3.6 MRC-5: 10 |
24 | A549 MRC-5 |
Cell viability decrease. Apoptotic genes Bax, Casp3, Casp9, and miR-192 expression increase. Anti-apoptotic gene Bcl-2 expression decrease. Cell cycle shift to sub-G1 phase. Antioxidant activity. Fewer effects on normal cells (MRC-5). Fragmentation of the genomic DNA. |
Concentration-, and Cell-Type dependent. | [52] |
| Toxicodendron vernicifluum | 2–40 | 5, 10, 20, 40, 80, 160, 320 | A549: >320 NiH3T3: 160 |
24 | A549 NIH3T3 |
Cell viability decreased on A549 but not on mouse embryo cells. ROS mediated apoptosis on A549. 95% Cell death at the maximum concentration for A549. |
Concentration-, and Cell type-dependent. | [53] |
| Citrate | 10, 75 | 1 | Not specified | 144 | BEAS-2B | 719 down-regulated and 998 up-regulated genes after exposure. DNA damage, Cell cycle arrest on G1. Fibrosis induction. EMT (epithelial-mesenchymal transition). Cell transformation is indicative of an oncogenic phenotype. |
Concentration-, Size-dependent-, and Time-dependent. |
[14] |
| Citrate | 60 | 50, 100, 200 | 200 μg Ag/mL | 24 | A549 HPSAEpiC |
Lysosomal pH alkalization (dysfunction) and autophagosome formation. Inhibition of autophagic flux. Inhibition of Transcriptional Factor EB (TFEB) expression. Concentration-dependence increase of p62 and LC3B-II proteins. |
Concentration-, And Cell type-dependent. |
[54] |
| Citrate, chitosan | 7–10 | 6.25 × 1012, 1.25 × 1012, 2.5 × 1012, 5 × 1012 NPs/mL | NHBE: 0.7 μg/cm2 A549 and BEAS-2B: not in range |
0.5, 4, and 24 hours | A549. BEAS-2B. NHBE. |
No cytotoxicity was observed on A549 and NHBE; not responsive to Transepithelial/transendothelial electrical resistance (TEER) change. Higher cytotoxicity resistance for NHBE compared with the other cells. ROS production is most prominent in A549. |
Concentration-, Cell type-, and Coating dependent |
[55] |
| Citrate | 10, 75 | 2 and 10 | 10 | 24 and 48 | HLF-1 | Decrease in cell viability. Reduction of metabolic activity. Procollagen and proinflammatory cytokine secretion. |
Time-dependent-, Concentration-, and size-dependent |
[28] |
| Uncoated | 4.7, 42 | 0.84–2000 | 4.7 nm: 7700 42 nm: 1150,000 |
24 | HbPF | Decrease in HPF viability. Reduction in cell mitochondrial activity and LDH leakage. ROS production and oxidative stress. No statistically significant changes in SOD activity. GSH depletion. |
Size-dependent. | [56] |
| Co-cultures | ||||||||
| Starch | 20 ± 4 | 7.25 μg, 41.25 μg (Nebulization) |
Out of range | 24 | hAELVi and THP-1 | High viability. Problems with determination. |
Concentration-, and Cell type-dependent. |
[57] |
| Garcinia mangostana | 12 | 2.5 μg/mL | Out of range | 24 | A549 with BEAS-2B | Cell viability decreased for A549. BEAS-2B is highly resistant. |
Cell type-dependent. | |
| Tannic acid | 50 ± 4 | 3 mg/L, 30 mg/L | Out of range | 24 | Calu-3, EA.hy926, and THP-1 | High toxicity at high concentration treatment. Pro-inflammatory markers IL-6, IL-8, and TNF-α significant secretion reduction. |
Cell type-, and Concentration-dependent. |
[58] |
| 3D-cultures | ||||||||
| Uncoated | 14 | 1.5, 4.4 and 13.2 ng/cm2. | LDH (not specified) | 6 and 24 | Organotypic-reconstituted 3D human primary small airway epithelial cell | Neutrophil accumulation. Macrophage levels modestly increased. SLC26A4 mucin gene production overexpressed. Duox1 expression increased (Small airway epithelial repair and bronchiolar re-epithelialization). Ect2, sftpa1, sftpd, muc1, and cftr epithelial-specific genes increase. MT1A and MT2A were upregulated (Cellular defense systems are in place to mitigate the effects of metal ion exposure), and metal overload. mir146, mir155, mir21 and mir224 (inflammatory process). NOXO1 and SOD2 ROS, mitochondrial disruption, DNA damage, cell cycle regulation, G2/M phase cell cycle arrest. The inflammatory process, Immunomodulatory response, and tissue remodeling. |
Concentration-dependent. | [59] |
| Uncoated | 20, 200 | 0.05, 0.5, 5 μg/cm2 | Out of range | 6 and 24 | 3D model representative of the alveolar barrier | ROS, cell death Increased level of mRNA Antioxidant and anti-inflammatory HMOX-1. Nuclear translocation of the transcription factor NF-kB in endothelial cells. Inflammation, increase in the mRNA levels of IL-6 and IL-8. |
Concentration-, and Size-dependent. |
[60] |
| PVP | 10–20 | 40 | Out of range | 24 | 3D and 2D A549 model | Apoptosis/Necrosis No effects on p53, Bax, and Caspase-3. Slightly reduced expression of Bcl-xL and NF-kB genes. Cells within 3D cultures were less affected by nanomaterials than in 2D cell cultures. Less affected when combined with hydra protein (ROS entrapment). |
Concentration-, size-, and Model-dependent. | [27] |
A549: human lung carcinoma (epithelial); BEAS-2B: human bronchial epithelium (normal); Calu-1: human lung epidermoid carcinoma (non-small-cell lung cancer); Calu-3: human lung adenocarcinoma (bronchial epithelial cells); EA.hy926: endothelial cells from the human umbilical vein; hAELVi: human alveolar epithelial cells; HLF-1: human lung fibroblast; HPF: primary cultures of pulmonary human fibroblasts; HPSAEpiC: human small airway epithelial cells; MRC-5: human fetal lung (male, normal); NCI-H 358: bronchoalveolar carcinoma (non-small-cell lung cancer); NG: natural gum; NHBE: normal human bronchial epithelial cells; NHLF: normal human lung fibroblast; NIH3T3: mouse Swiss NIH embryo (fibroblast); NS: not specified; THP-1: human acute monocytic leukemia; TKP: tamarind kernel powder; Wi38: human fetal lung (female, normal).