Table 2.
Cytotoxicity of TiO2 particles with different structural features.
| Structural Feature | Cell Line | Dose and Exposure Time | Cytotoxicity Effect | Reference |
|---|---|---|---|---|
| Ultrafine TiO2 (29 nm mean diameter, 50 m2/g surface area), fine TiO2 (250 nm mean diameter, 6.6 m2/g surface area) | Macphage cell line (J774.2) | 125.45 mg/mL for 4, 8, 24, and 48 h | Ultrafine and fine particles had no significant cytotoxic effects on J774.2 AM ultrafine TiO2 significantly impair the ability of J774.2 mouse AM to phagocytose 2 μm indicator latex beads more than the fine TiO2. | [33] |
| 27 nm TiO2 particles | Human bronchial epithelial cells (BEAS 2B) | 27 nm TiO2 was internalized into BEAS-2B cells and proximity to cellular nuclei between 5 min and 2 h. | [35] | |
| Nanosized TiO2 particles (10 and 20, 200 nm) | BEAS 2B | Nanosized TiO2 particles (10 and 20 nm) induced the oxidative DNA damage, lipid peroxidation, and micronuclei formation in the absence of light, but larger sized TiO2 (>200 nm) did not induce any oxidative stress and DNA damaging events; rutile-sized 200 nm particles induced hydrogen peroxide and oxidative DNA damage in the absence of light but the anatase-sized 200 nm particles did not. | [38] | |
| Spherical TiO2 NPs (12–140 nm; both anatase and rutile) | Human lung carcinoma epithelial cell line (A549 cells) | Single strand breaks, oxidative lesions to DNA and oxidative stress were induced; the cells ability to repair DNA was impaired. | [51,52] | |
| TiO2-based nanofilaments | Human lung tumor cells (H596) | 0.01, 0.1, 1, and 2 μg/mL | TiO2-based nanofilaments (2 μg/mL) impaired cell proliferation and cell death in a dose-dependent manner; The short (<5 μm) needle-like structures were taken up by H596 cells and clustered and gathered around the cell nucleus. | [53] |
| TiO2 nanobelts: short (<5 μm) long (>15 μm) | Primary murine alveolar macrophages | 100 μg/mL | The 15-μm nanobelts were highly toxic, involving the loss of lysosomal integrity and the release of cathepsin B. These fiber-shaped nanomaterials induced inflammasome activation and the release of inflammatory cytokines in a manner very similar to asbestos or silica. | [54] |
| 0-D TiO2 nanoparticles, 1-D TiO2 nanorods, 3-D TiO2 assemblies | HeLa cells | 125 μg/mL | 0-D anatase NPs decreased cell viability to a level of 80% at 125 μg/mL, and cell viability of 1-D and 3-D structures remained close to 100%; 0-D TiO2 NPs and 1-D nanorods could be readily internalized into the cells and the spherical particles were taken up more than the rod-shaped particles of similar size; 3-D assembled aggregates of TiO2 were less likely to be incorporated into cells. | [55] |
| Anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), anatase nanobelts (TiO2-NBs) | Human monocyte/macrophage cell line (THP-1) | 10, 25, 50, and 100 μg/mL for 24 h | TiO2 was not cytotoxic except for the nanobelt form, which was cytotoxic and induced significant IL-1β production in THP-1 cells. | [56] |
| Anatase and rutile TiO2 NPs | A549 | Anatase TiO2 produced greater cell responses and was more toxic than rutile by MTT and XTT assay. Differences in biological response of NPs occurred as a function of size, crystalline phase and chemical composition. | [57] | |
| Nanocrystalline TiO2 (anatase and rutile) | A549 and human dermal fibroblasts (HDF) cell line | 100 μg/mL | Anatase was 2 orders of magnitude more cytotoxic (LC50 of 3.6 µg/mL) than similarly sized rutile counterparts (LC50 of 550 µg/mL) by determining cell viability and LDH release; The most cytotoxic NPs were the most effective for generating ROS, and were more likely to generate damaging RS species in cell culture. | [58] |
| Nanosized anatase (<25 nm), nano-sized rutile with SiO2 coating, and fine rutile (<5 µm) | BEAS-2B, Chinese hamster lung fibroblast (V79) cells | 1–100 μg/cm2 for 24, 48, and 72 h | Nano-sized anatase and fine rutile induced DNA damage at doses of 1 and 10 μg/cm2, while SiO2-coated rutile induced DNA damage only at 100 μg/cm2. Only nanosized anatase could elevate the frequency of micronucleated BEAS-2B cells. | [59,60] |
| Anatase and rutile TiO2 NPs (6.3, 10, 50, and 100 nm) | Mouse keratinocyte cell line (HEL-30) | 0, 10, 25, 50, 100, and 150 μg/mL for 24 h | Anatase TiO2 NPs could induce cell necrosis, whereas rutile TiO2 NPs could initiate apoptosis through the formation of ROS. | [61] |
| Uncoated TiO2 (anatase and rutile), polyacrylate-coated nano-TiO2 | Chinese hamster lung fibroblast (V79) cells | 10 and 100 mg/L for 24 h | Both coated and uncoated TiO2 (anatase and rutile) decreased the cell viability in a mass- and size-dependent manner; TiO2 NPs coated with polyacrylate were only cytotoxic at high concentration (100 mg/L), and only uncoated nano-TiO2 induced DNA damage. | [60] |
| Functionalized TiO2 NPs with various surface groups (–OH, −NH2, and –COOH) | Lewis lung carcinoma, 3T3 fibroblasts | 0.01, 0.1, 1, and 10 mg/L for 24 h | –NH2 and –OH groups showed significantly higher toxicity than –COOH; the decreased cell viability was associated with TiO2 particles-induced protein aggregation/denaturation and subsequent impaired cell membrane function. | [62] |
| Rutile (<5 μm), nanosized rutile/anatase (~30 nm), nanosized anatase (<25 nm), silica-coated nanosized needle-like rutile (~10 × 40 nm) (cnTiO2) | Murine macrophages RAW 264.7; Human pulmonary fibroblasts (MRC-9) | 20, 30, 100, 300 μg/mL for 6 h | cnTiO2 elicited significant induction of TNF-α and neutrophil-attracting chemokines. Stimulation of human fibroblasts with cnTiO2-activated macrophage supernatant induced high expression of neutrophil-attracting chemokines, CXCL1 and CXCL8. | [45] |
| Pure anatase and rutile TiO2 | Human alveolar type-I-like epithelial cell (TTI) | These two nano-TiO2 forms mediated a similar profile and pattern of inflammatory response; pure rutile caused a small, but consistently greater response for IL-6, IL-8 and MCP-1; the temporal induction of oxidative stress varied markedly between the two nano-TiO2 forms. | [63] |