Length-dependent toxicity of TiO₂ nanofibers: mitigation via shortening

Abstract

A mitigation strategy for the toxicity of TiO 2 nanofibers: high aspect ratio reduction Length and aspect ratio represent important toxicity determinants of fibrous nanomaterials. We have previously shown that anatase TiO 2 nanofibers (TiO 2 NF) cause a dose-dependent decrease of cell viability as well as the loss of epithelial barrier integrity in polarized airway cell monolayers. Herein we have investigated the impact of fiber shortening, obtained by ball-milling, on the biological effects of TiO 2 NF. Long TiO₂ NF (L-TiO 2 NF) were more cytotoxic than their shortened counterparts (S-TiO 2 NF) towards alveolar A549 cells and bronchial 16HBE cells. Moreover, L-TiO 2 NF affected the trans-epithelial electrical resistance of 16HBE monolayers. This effect was associated with altered distribution of tight-junction proteins and also mitigated by fiber shortening. Macrophages efficiently internalized S-TiO 2 NF but not L-TiO 2 NF, which caused cell stretching and deformation. In macrophages S-TiO 2 NF enhanced the expression of pro-inflammatory genes, NO production and cytokine secretion, which was significantly inhibited by the phagocytosis inhibitor cytochalasin B. In vivo experiments indicated length-dependent toxicity in both the lungs and peritoneal cavity of mice, leading to significant increase in markers of inflammation in animals treated with L-TiO 2 NF. It is concluded that fiber shortening mitigates NF detrimental effects on cell viability and epithelial barrier competence in vitro as well as the increase of inflammatory cytokines and granulocytes influx upon in vivo exposure. These data suggest that fiber shortening may represent an effective safe-by-design strategy for mitigating TiO 2 NF toxic effects both in vitro and in vivo.

Emissions and exposures of graphene nanomaterials, titanium dioxide nanofibers, and nanoparticles during down-stream industrial handling

“…They appear to be present in the workplace air as bundles, and some of the fibers detected by SEM during Study B were at least 5 µm and could therefore constitute a risk if inhaled. Bianchi et al [58] have recently shown that long (around 10 µm) TiO 2 NFs induce cell cytotoxicity in vitro and inflammation in vivo, while shortened (around 2 µm) TiO 2 NFs seem to mitigate the toxic effects, even without macrophages present in the in vitro cultures. SEM-analysis can also be used to quantify the particle concentration in the air.…”

Cytotoxicity of Metal‐Based Nanoparticles: From Mechanisms and Methods of Evaluation to Pathological Manifestations

“…TiO 2 exposure can cause a marked and widespread perturbation of the distribution of claudin-7 (red in the online version) and ZO-1 (green in the online version). Reproduced with permission [191]. Copyright 2020, Taylor & Francis Group.…”

Comparison of P25 and nanobelts on Kruppel‐like factor‐mediated nitric oxide pathways in human umbilical vein endothelial cells

“…When applied to HUVECs, the cells apparently internalized more nanobelts compared with P25 at the same mass concentrations (Figure 4), indicating that the morphologies of TiO 2 materials altered their interactions with HUVECs. Previous studies also demonstrated that the different physicochemical properties of metal oxide based NMs altered their interactions with cells (Bianchi et al, 2020; Déciga‐Alcaraz et al, 2020; Jain et al, 2017; Medina‐Reyes et al, 2020; Simon et al, 2017). However, despite much higher internalization, P25 or nanobelts did not obviously lower cellular viability as measured by CCK‐8 and neutral red uptake assays (Figure 3), consistent with the point that Ti is a relatively biocompatible element (Luo et al, 2020; Wang, Zhong, Li, et al, 2021).…”