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Review Article | Open Access

Incidental vs. engineered nanoparticles in Alzheimer’s and Parkinson’s disease: Pathological pathways and therapeutic interventions

Hanyu Li1,2,§Ning Wang1,2,§Xiaobo Mao1,2,3,4,5 ( )
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21211, USA
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21211, USA

§ Hanyu Li and Ning Wang contributed equally to this work.

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Abstract

Nanoparticles (NPs) play dual roles in neurodegeneration. Incidental NPs, generated unintentionally from environmental and industrial sources, are linked to oxidative stress, neuroinflammation, and disruption of the blood–brain barrier in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Engineered NPs are designed for diagnosis and therapy using nanobodies, nanozymes, and other engineered nanoparticle (ENP) platforms that enable targeted delivery, modulation of neuroimmune pathways, and interference with pathological protein aggregation. This review aligns source-based classes (incidental versus engineered) with composition-based families (metal-based, carbon-based, and polymeric or inorganic), and summarizes routes of exposure, mechanistic toxicology, and engineered interventions relevant to AD and PD. We also evaluate current limitations, including biocompatibility, relevance to chronic exposure, and clinical benchmarking, and we outline priorities for translating nanotechnology into practical diagnostics and therapeutics for neurodegenerative disease.

Graphical Abstract

This comprehensive review explores the dualistic nature of nanoparticle interactions with the brain, integrating current evidence on their therapeutic potential—particularly via nanozymes and engineered nanocarriers—as well as their neurotoxic risks, with a central focus on how these mechanisms influence the pathogenesis and intervention strategies for Alzheimer’s and Parkinson’s diseases.

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Nano Research
Article number: 94908055

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Cite this article:
Li H, Wang N, Mao X. Incidental vs. engineered nanoparticles in Alzheimer’s and Parkinson’s disease: Pathological pathways and therapeutic interventions. Nano Research, 2025, 18(11): 94908055. https://doi.org/10.26599/NR.2025.94908055
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Received: 10 May 2025
Revised: 07 September 2025
Accepted: 09 September 2025
Published: 20 October 2025
© The Author(s) 2025. Published by Tsinghua University Press.

This is an open access article under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0, https://creativecommons.org/licenses/by/4.0/).