Spin-driven enantioselective regulation of cyclooxygenase-2 activity for rheumatoid arthritis therapy via chiral gold nanohelices.

Yan, Jiao; Liu, Lai; Chen, Zhihao; Zhao, Qian; Han, Xiaoqing; Wang, Yanjing; Mu, Zhengzhi; Wang, Xingbo et al. · Nat Commun · 2026

basic_science · Level V

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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 (<sub>C</sub>Au) 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 <sub>C</sub>Au, we demonstrate that left-handed <sub>C</sub>Au (Lh-<sub>C</sub>Au) enhances, whereas right-handed <sub>C</sub>Au (Rh-<sub>C</sub>Au) 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 <sub>C</sub>Au (<sub>C</sub>Au@MIP) for selectively regulating COX-2 in inflammatory cells and collagen-induced arthritis murine model (male DBA/1 J mice). Treatment with Rh-<sub>C</sub>Au@MIP significantly reduces prostaglandin E<sub>2</sub> 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.