Effect of Titanium Dioxide Nanoparticles on Mammalian Cell Cycle In Vitro: A Systematic Review and Meta-Analysis

Abstract

Although most studies that explore the cytotoxicity of titanium dioxide nanoparticles (nano-TiO2) have focused on cell viability and oxidative stress, the cell cycle, a basic process of cell life, can also be affected. However, the results on the effects of nano-TiO2 on mammalian cell cycle are still inconsistent. A systematic review and meta-analysis were therefore performed in this research based on the effects of nano-TiO2 on the mammalian cell cycle in vitro to explore whether nano-TiO2 can induce cell cycle arrest. Meanwhile, the impact of physicochemical properties of nano-TiO2 on the cell cycle in vitro was investigated, and the response of normal cells and cancer cells was compared. A total of 33 articles met the eligibility criteria after screening. We used Review Manager 5.4 and Stata 15.1 for analysis. The results showed an increased percentage of cells in the sub-G1 phase and an upregulation of the p53 gene after being exposed to nano-TiO2. Nevertheless, nano-TiO2 had no effect on cell percentage in other phases of the cell cycle. Furthermore, subgroup analysis revealed that the cell percentage in both the sub-G1 phase of normal cells and S phase of cancer cells were significantly increased under anatase-form nano-TiO2 treatment. Moreover, nano-TiO2 with a particle size <25 nm or exposure duration of nano-TiO2 more than 24 h induced an increased percentage of normal cells in the sub-G1 phase. In addition, the cell cycle of cancer cells was arrested in the S phase no matter if the exposure duration of nano-TiO2 was more than 24 h or the exposure concentration was over 50 μg/mL. In conclusion, this study demonstrated that nano-TiO2 disrupted the cell cycle in vitro. The cell cycle arrest induced by nano-TiO2 varies with cell status and physicochemical properties of nano-TiO2.

Surface modification of TiO2 nanoparticles with organic molecules and their biological applications

“…Besides, this type of surface modification can reduce the potential toxicity of unmodified TiO 2 NPs, which is reported in recent publications. 5 In the following, some recent publications will be presented in which the TiO 2 NPs have been modified with such types of organic modifiers to prepare the efficient therapeutic TiO 2 NPs.…”

“…Besides, this type of surface modification can reduce the potential toxicity of unmodified TiO 2 NPs, which is reported in recent publications. 5 In the following, some recent publications will be presented in which the TiO 2 NPs have been modified with such types of organic modifiers to prepare the efficient therapeutic TiO 2 NPs. The surface modification of TiO 2 NPs with organic dyes, especially porphyrins, has attracted growing interest as it can broaden the absorption range of TiO 2 NPs from the UV region to the visible region.…”

“…14 For these applications, an appropriate surface modification of TiO 2 NPs is required to improve their physicochemical properties and biological effectiveness and, more importantly, decrease their potential toxicity in mammalian cells. 5 The surface modification not only prevents the agglomeration of TiO 2 NPs but also provides the possibility for further functionalization/conjugation. The modification of TiO 2 NPs can be achieved using two different approaches: non-covalent and covalent conjugation of organic (or inorganic) species with TiO 2 NPs.…”

“…Regarding their industrial importance, the global market size of TiO 2 NPs was estimated to be $1.1 billion in 2021, and forecasted to have a compound annual growth rate of 6.5% until 2026, with annual production predicted to reach 2.5 million tons by 2025. 5,6 In the biomedical fields, TiO 2 NPs are frequently studied for photodynamic therapy, 1,7 drug delivery, 8 antimicrobial applications, 3,[9][10][11][12] biosensors, 13 and tissue engineering. 14 For these applications, an appropriate surface modification of TiO 2 NPs is required to improve their physicochemical properties and biological effectiveness and, more importantly, decrease their potential toxicity in mammalian cells.…”

Impact of nano-titanium dioxide extracted from food products on Caco-2 cells using three-phase digestion model

“…8,10,[12][13][14] At higher concentrations, TiO 2 nanoparticles cause reproductive toxicity in both females and males, [15][16][17] and induce oxidative stress that leads to cell damage, inflammation, and adverse immune responses. 9,11,12,17 Systematic review and metaanalysis have demonstrated that TiO 2 nanoparticles disrupt the mammalian cell cycle in vitro, 18 and disturb glucose and lipid homeostasis in mice and rats. 11,12 The nanomaterial has also been found to impact the digestive tract, increasing chronic intestinal inflammation and disorders of the intestinal barrier, and disrupting the normal functions of the gastrointestinal tract.…”