Abstract
Electron-spin dynamics represent an additional dimension in enzymatic catalysis, where most regulatory strategies focus on modulating active-site chemistry. Here, we present a spintronic approach that employs chiral gold nanohelices (CAu) as electron spin polarizers to enantiospecifically modulate cyclooxygenase-2 (COX-2) activity for rheumatoid arthritis intervention. Exploiting the chirality-induced spin selectivity (CISS) effect inherent to both COX-2 and CAu, we demonstrate that left-handed CAu (Lh-CAu) enhances, whereas right-handed CAu (Rh-CAu) suppresses COX-2 catalytic efficiency via spin-dependent electron transfer at the chiral nanoparticle-enzyme interfaces. To achieve targeted modulation in complex biological settings, we engineer molecularly imprinted CAu (CAu@MIP) for selectively regulating COX-2 in inflammatory cells and collagen-induced arthritis murine model (male DBA/1 J mice). Treatment with Rh-CAu@MIP significantly reduces prostaglandin E2 secretion and mitigates joint inflammation, achieving therapeutic efficacy comparable to conventional COX-2 inhibitors. Our findings introduce electron spin polarization as an orthogonal mechanism for enzymatic regulation, offering a bioelectronic strategy for inflammation-targeted therapy.
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Data availability
All data supporting the findings of this study are included in the article and Supplementary Information files. Source data are provided as a Source data file. The full image dataset is available from the corresponding author upon request. Source data are provided with this paper.
Code availability
The MATLAB (version R2021b) and Python (version 3.13.9) codes used for theoretical simulations in this study are available in the website of https://doi.org/10.6084/m9.figshare.30391330.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (32301181, J.Y.; 22077119, H.Z.; 12274466, 11874428, A.G.; 11921005, 12374034, Q.S.), the National Key Research and Development Program of China (2021YFE0100300, 2021YFF0704805, H.Z.), Science and Technology Development Program Project of Jilin Province (20240101188JC, J.Y.), the Hunan Provincial Science Fund for Distinguished Young Scholars (2023JJ10058, A.G.), the High Performance Computing Center of Central South University, and the Nanshan Scholar Start-up Fund of Guangzhou Medical University (06-445-1119, J.Y.; 06-445-1187, H.Z.). We also sincerely thank Zeng-Ren Liang for useful help on programming.
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J.Y. conceived and designed the project; L.L., Q.Z., A.G., and Q.S. performed the theoretical calculation; J.Y., Z.C., X.W., Y.K., and X.H. collected animal data; Y.W., P.S. conducted cell data collection and analysis; Z.M. measured and analyzed the electrochemistry data; J.Y., A.G., Q.S., and H.Z. wrote the paper; H.Z. supervised the project. All authors reviewed and revised the manuscript. J.Y., L.L. contributed equally.
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Yan, J., Liu, L., Chen, Z. et al. Spin-driven enantioselective regulation of cyclooxygenase-2 activity for rheumatoid arthritis therapy via chiral gold nanohelices. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71522-9
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DOI: https://doi.org/10.1038/s41467-026-71522-9
