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. 2020 Jun 10:8:575.
doi: 10.3389/fbioe.2020.00575. eCollection 2020.

Toxicity Evaluation of TiO2 Nanoparticles on the 3D Skin Model: A Systematic Review

Priscila Laviola Sanches  1   2 , Luths Raquel de Oliveira Geaquinto  2   3 , Rebecca Cruz  4 , Desirée Cigaran Schuck  5 , Márcio Lorencini  5 , José Mauro Granjeiro  1   2   3   4 , Ana Rosa Lopes Ribeiro  1   3
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Toxicity Evaluation of TiO2 Nanoparticles on the 3D Skin Model: A Systematic Review

Priscila Laviola Sanches et al. Front Bioeng Biotechnol. .

Abstract

Titanium dioxide nanoparticles (TiO2 NPs) are regularly used in sunscreens because of their photoprotective capacity. The advantage of using TiO2 on the nanometer scale is due to its transparency and better UV blocking efficiency. Due to the greater surface area/volume ratio, NPs become more (bio)-reactive giving rise to concerns about their potential toxicity. To evaluate the irritation and corrosion of cosmetics, 3D skin models have been used as an alternative method to animal experimentation. However, it is not known if this model is appropriate to study skin irritation, corrosion and phototoxicity of nanomaterials such as TiO2 NPs. This systematic review (SR) proposed the following question: Can the toxicity of TiO2 nanoparticles be evaluated in a 3D skin model? This SR was conducted according to the Preliminary Report on Systematic Review and Meta-Analysis (PRISMA). The protocol was registered in CAMARADES and the ToxRTool evaluation was performed in order to increase the quality and transparency of this search. In this SR, 7 articles were selected, and it was concluded that the 3D skin model has shown to be promising to evaluate the toxicity of TiO2 NPs. However, most studies have used biological assays that have already been described as interfering with these NPs, demonstrating that misinterpretations can be obtained. This review will focus in the possible efforts that should be done in order to avoid interference of NPs with biological assays applied in 3D in vitro culture.

Keywords: 3D skin model; alternative method; nanoparticles; titanium dioxide; toxicity.

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Figures

Figure 1
Figure 1
Different pathways of nanoparticle penetration. Paracellular transport (between cells), transcellular transport (inside the cells), transport by hair follicles, sweat glands, skin folds or a combination of all. Image adapted from: https://smart.servier.com.
Figure 2
Figure 2
Scheme of the main 3D skin models used. Image adapted from https://smart.servier.com.
Figure 3
Figure 3
Flow diagram of literature selection process, from Moher et al. (2009).
Figure 4
Figure 4
Toxicological assays. (A) Physico-chemical characteristics of NPs TiO2 NPs that possible interfere with the biological assays; that include (B) optical capabilities of TiO2 NPs such as intrinsic absorbance and/or fluorescence (b1); adsorption of proteins, salts and dyes (s) to NPs (b2); and dissolution of NPs with the consequent release of metal ions to supernatant (b3). (C) Conventional MTT test analyzing TiO2 NPs demonstrating that NPs can adsorb to MTT dye that avoid metabolization of reagents. Image adapted from: https://smart.servier.com.
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