Neurotoxicity of Titanium Dioxide Nanoparticles: A Comprehensive Review

Abstract The increasing use of titanium dioxide nanoparticles (TiO2 NPs) across various fields has led to a growing concern regarding their environmental contamination and inevitable human exposure. Consequently, significant research efforts have been directed toward understanding the effects of TiO2 NPs on both humans and the environment. Notably, TiO2 NPs exposure has been associated with multiple impairments of the nervous system. This review aims to provide an overview of the documented neurotoxic effects of TiO2 NPs in different species and in vitro models. Following exposure, TiO2 NPs can reach the brain, although the specific mechanism and quantity of particles that cross the blood-brain barrier (BBB) remain unclear. Exposure to TiO2 NPs has been shown to induce oxidative stress, promote neuroinflammation, disrupt brain biochemistry, and ultimately impair neuronal function and structure. Subsequent neuronal damage may contribute to various behavioral disorders and play a significant role in the onset and progression of neurodevelopmental or neurodegenerative diseases. Moreover, the neurotoxic potential of TiO2 NPs can be influenced by various factors, including exposure characteristics and the physicochemical properties of the TiO2 NPs. However, a systematic comparison of the neurotoxic effects of TiO2 NPs with different characteristics under various exposure conditions is still lacking. Additionally, our understanding of the underlying neurotoxic mechanisms exerted by TiO2 NPs remains incomplete and fragmented. Given these knowledge gaps, it is imperative to further investigate the neurotoxic hazards and risks associated with exposure to TiO2 NPs.

• Publication year

  2023

• Venue

  International Journal of Nanomedicine

• Publication date

  2023-12-01

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.2147/IJN.S442801PMID 38076727PMCID 10710240
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2022cited by this paper
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  2022influential reference
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  2022cited by this paper
• Prenatal titanium exposure and child neurodevelopment at 1 year of age: A longitudinal prospective birth cohort study.

  2022cited by this paper
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  2022cited by this paper
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  2022cited by this paper
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  2022cited by this paper
• Thermal stress and TiO2 nanoparticle–induced oxidative DNA damage and apoptosis in mouse hippocampus

  2022cited by this paper
• Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling

  2022cited by this paper
• Titanium Dioxide: Structure, Impact, and Toxicity

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• Prenatal exposure to titanium dioxide nanoparticles induces persistent neurobehavioral impairments in maternal mice that is associated with microbiota-gut-brain axis.

  2022cited by this paper
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  2022cited by this paper
• Developmental titanium dioxide nanoparticle exposure induces oxidative stress and neurobehavioral changes in zebrafish.

  2021cited by this paper
• Acute titanium dioxide nanoparticles exposure impaired spatial cognitive performance through neurotoxic and oxidative mechanisms in Wistar rats

  2021cited by this paper
• Role of necroptosis of alveolar macrophages in acute lung inflammation of mice exposed to titanium dioxide nanoparticles

  2021cited by this paper
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  2021cited by this paper
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  2021cited by this paper
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  2021cited by this paper
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  2021cited by this paper
• Developmental co-exposure of TBBPA and titanium dioxide nanoparticle induced behavioral deficits in larval zebrafish.

  2021cited by this paper
• Developmental Toxicity of the Neural Tube Induced by Titanium Dioxide Nanoparticles in Mouse Embryos

  2021cited by this paper
• Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring

  2021cited by this paper
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  2021cited by this paper
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  2021cited by this paper
• Effects of Prenatal Exposure to Titanium Dioxide Nanoparticles on DNA Methylation and Gene Expression Profile in the Mouse Brain

  2021cited by this paper
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  2021cited by this paper
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  2021cited by this paper
• Titanium dioxide nanoparticle affects motor behavior, neurodevelopment and axonal growth in zebrafish (Danio rerio) larvae.

  2021cited by this paper
• Toxicity mechanisms of selected engineered nanoparticles on human neural cells in vitro.

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  2020cited by this paper
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  2020cited by this paper
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  2020cited by this paper
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  2020cited by this paper
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  2020cited by this paper
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  2020cited by this paper
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  2020cited by this paper
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  2020cited by this paper
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  2020cited by this paper
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  2020cited by this paper
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  2019cited by this paper
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  2019cited by this paper
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  2019cited by this paper
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• The effect of titanium dioxide nanoparticles on neuroinflammation response in rat brain

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• In vitro screening of metal oxide nanoparticles for effects on neural function using cortical networks on microelectrode arrays

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• TiO2 nanoparticles-induced apoptosis of primary cultured Sertoli cells of mice.

  2016cited by this paper
• Microglial M1/M2 polarization and metabolic states

  2016cited by this paper
• Dynamic Probabilistic Modeling of Environmental Emissions of Engineered Nanomaterials.

  2016cited by this paper
• Mechanism of TiO2 nanoparticle‐induced neurotoxicity in zebrafish (Danio rerio)

  2016cited by this paper
• Genotoxicity Studies of Titanium Dioxide Nanoparticles (TiO2NPs) in the Brain of Mice

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  2026cites this paper
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