Zinc Oxide Nanoparticle-Induced Neurotoxicity: Underlying Molecular Mechanisms and Future Perspectives

Chen, Chun; Pei, Xingyao; Yu, Yonger; Gao, Chang; Wang, Jinran; Zhu, Rongyao; Liu, Shuxuan; Tang, Shusheng; Li, Daowen

doi:10.3390/toxics14010011

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Zinc Oxide Nanoparticle-Induced Neurotoxicity: Underlying Molecular Mechanisms and Future Perspectives

by

Chun Chen

^1,2,3,†

,

Xingyao Pei

^2,†,

Yonger Yu

²,

Chang Gao

²,

Jinran Wang

²,

Rongyao Zhu

²,

Shuxuan Liu

²,

Shusheng Tang

^1,3,*

and

Daowen Li

^2,*

¹

State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China

²

Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300384, China

³

Technology Innovation Center for Food Safety Surveillance and Detection (Hainan), Sanya Institute of China Agricultural University, Sanya 572025, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Toxics 2026, 14(1), 11; https://doi.org/10.3390/toxics14010011 (registering DOI)

Submission received: 23 November 2025 / Revised: 16 December 2025 / Accepted: 18 December 2025 / Published: 20 December 2025

(This article belongs to the Special Issue Toxicity of Zinc Oxide Nanoparticles: Mechanism Exploration and Risk Assessment)

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Abstract

The expanding application of zinc oxide nanoparticles (ZnO NPs) in consumer products, medicine, and the food industry has raised significant concerns regarding their potential neurotoxicity. This review synthesizes current understanding of the pathways by which ZnO NPs gain access to the central nervous system (CNS), their resulting neurotoxic effects, and the underlying molecular mechanisms. These nanoparticles primarily breach the CNS via translocation across the blood–brain barrier, axonal transport along sensory nerves, and disruption of the microbiota–gut–brain axis. Upon entry, ZnO NPs induce behavioral deficits, including impaired learning, memory, and motor function, alongside pathological brain damage. The neurotoxicity is driven by a multi-faceted mechanism involving mitochondrial dysfunction, oxidative stress, energy depletion, and neuroinflammation, often triggered by the release of Zn²⁺ ions. Furthermore, ZnO NPs can activate diverse cell death pathways, including apoptosis, ferroptosis, and pyroptosis. Critically, their neurotoxic potential is intrinsically linked to their physicochemical properties, such as size and shape. Emerging evidence also suggests that ZnO NP exposure may promote the aggregation of pathological proteins like Tau, thereby potentially increasing the risk for neurodegenerative diseases. Finally, we discuss potential mitigation strategies, such as surface modification and intervention with natural compounds. This review underscores the need for a refined risk assessment of ZnO NPs to ensure their safe deployment.

Keywords: zinc oxide nanoparticles; neurotoxicity; risk assessment; protective agent

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MDPI and ACS Style

Chen, C.; Pei, X.; Yu, Y.; Gao, C.; Wang, J.; Zhu, R.; Liu, S.; Tang, S.; Li, D. Zinc Oxide Nanoparticle-Induced Neurotoxicity: Underlying Molecular Mechanisms and Future Perspectives. Toxics 2026, 14, 11. https://doi.org/10.3390/toxics14010011

AMA Style

Chen C, Pei X, Yu Y, Gao C, Wang J, Zhu R, Liu S, Tang S, Li D. Zinc Oxide Nanoparticle-Induced Neurotoxicity: Underlying Molecular Mechanisms and Future Perspectives. Toxics. 2026; 14(1):11. https://doi.org/10.3390/toxics14010011

Chicago/Turabian Style

Chen, Chun, Xingyao Pei, Yonger Yu, Chang Gao, Jinran Wang, Rongyao Zhu, Shuxuan Liu, Shusheng Tang, and Daowen Li. 2026. "Zinc Oxide Nanoparticle-Induced Neurotoxicity: Underlying Molecular Mechanisms and Future Perspectives" Toxics 14, no. 1: 11. https://doi.org/10.3390/toxics14010011

APA Style

Chen, C., Pei, X., Yu, Y., Gao, C., Wang, J., Zhu, R., Liu, S., Tang, S., & Li, D. (2026). Zinc Oxide Nanoparticle-Induced Neurotoxicity: Underlying Molecular Mechanisms and Future Perspectives. Toxics, 14(1), 11. https://doi.org/10.3390/toxics14010011

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Zinc Oxide Nanoparticle-Induced Neurotoxicity: Underlying Molecular Mechanisms and Future Perspectives

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