iProXProteomicsJiao YanMus Musculushttp://www.iprox.org/page/project.html?id=IPX0014572000yanjiao@gzhmu.edu.cnGuangzhou Medical UniversityiProXfalseSpin-driven Enantioselective Regulation of Cyclooxygenase-2 Activity for Rheumatoid Arthritis Therapy via Chiral Gold NanohelicesElectron-spin dynamics represent an unexplored 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 further engineering of molecularly imprinted CAu (CAu@MIP) for selectively regulating COX-2 in inflammatory cells and collagen-induced arthritis murine model. 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.Wed Apr 08 00:00:00 BST 2026PXD07674210090