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PEGylated protein nanoparticles for the inhibition of Aβ fibrillation via Aβ binding with minimal nonspecific protein interactions

Polymer Journal (2026) Cite this article

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Abstract

Amyloid-β (Aβ) fibrillation is a key pathological event in Alzheimer’s disease (AD), promoting the development of nanomaterial-based inhibitors that can function in protein-rich biological media. PEGylated nanoparticles are attractive for such applications because poly(ethylene glycol)(PEG) coronas suppress nonspecific protein adsorption and enhance colloidal stability; however, how PEG content influences Aβ fibrillation remains insufficiently understood. Here, we report how the degree of PEGylation modulates the inhibitory activity of protein-based nanoparticles toward Aβ fibrillation. We selected lysozyme (LYZ) as a model protein and synthesized PEG–LYZ conjugates bearing 3–10 PEG chains per protein (NPEG), followed by nanoparticle formation via a nanoemulsion method. PEG–LYZ conjugates with NPEG ≥ 5 formed colloidally stable nanoparticles. Compared with the molecular forms, nanoparticulation increased the apparent surface hydrophobicity of PEG–LYZ and enhanced the suppression of Aβ42 fibrillation. Among the series, the inhibitory activity of the PEG–LYZ(10) nanoparticles was the greatest, and the nanoparticles maintained their dispersibility after they interacted with Aβ42, as evidenced by ThT fluorescence assays together with TEM and DLS analyses. QCM measurements further indicated appreciable Aβ42 binding but only minimal adsorption of model proteins, which is consistent with antifouling behavior. These findings highlight PEG content as a key design parameter governing nanoparticle formation, Aβ inhibition, and nonspecific protein adsorption in PEGylated protein nanoparticles.

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Acknowledgements

This work was partly supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant numbers 21H05521, 22K12816, and 25K15909).

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Authors and Affiliations

  1. Faculty of Molecular Chemistry and Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan

    Tomonori Waku, Takashi Yoshikawa, Kazuya Matsuo & Akio Kobori

  2. Center for Social and Biomedical Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan

    Tomonori Waku

  3. Greentech Co. Ltd., 471 Santei-cho, Kamigyo-ku, Kyoto, 602-0915, Japan

    Michiaki Okuda & Hachiro Sugimoto

  4. Faculty of Life and Medical Sciences, Doshisha University, 1-3 Tatara Miyakodani, Kyotanabe, Kyoto, 610-0394, Japan

    Hachiro Sugimoto

Authors
  1. Tomonori Waku
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  4. Hachiro Sugimoto
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Correspondence to Tomonori Waku.

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Waku, T., Yoshikawa, T., Okuda, M. et al. PEGylated protein nanoparticles for the inhibition of Aβ fibrillation via Aβ binding with minimal nonspecific protein interactions. Polym J (2026). https://doi.org/10.1038/s41428-026-01175-4

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