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Precisely disrupting PLT\u2010mediated pathological cellular crosstalk has emerged as promising therapeutics. Existing PLT\u2010targeting strategies primarily rely on the ligand\u2010mediated recognition, overlooking the hemodynamic behavior of circulating PLTs. Under blood flow, PLTs preferentially roll along vascular walls, while conventional nanocarriers tend to flow along the central axis. This inherent spatial separation limits their targeting efficiency. The optimization of nanoparticle geometry provides a potential solution by enabling precise control over their flow trajectories in circulation. Herein, the study designs fucoidan\u2010functionalized nanoplatforms with different morphologies and comparatively explores their targeting efficiency and regulatory activity in PLTs. In a microfluidic flow model, rod\u2010shaped nanoparticles exhibit markedly enhanced co\u2010localization with endothelial\u2010adherent PLTs. Moreover, these rod\u2010shaped nanoparticles inhibit focal adhesion kinase (FAK) and PI3K\/AKT signaling in a morphology\u2010dependent manner, thereby effectively disrupting their pathological cellular crosstalk. In arthritic rats, intravenously administered resveratrol\u2010loaded nanorod (PNR@Res) efficiently binds circulating PLTs and accumulates in inflamed joints, ultimately effectively alleviating RA symptoms. The findings offer insight into how nanoparticle geometry governs cell interactions with circulating PLTs and influences PLT pathological behaviors through a morphology\u2010dependent mechanism in inflammatory diseases.<\/jats:p>","DOI":"10.1002\/advs.202518005","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T06:26:42Z","timestamp":1763706402000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rod\u2010Shaped Nanotherapeutics Alleviate Rheumatoid Arthritis by Precisely Disrupting Platelet\u2010Mediated Pathological Crosstalk via a Morphology\u2010Dependent Manner"],"prefix":"10.1002","volume":"13","author":[{"given":"Bin","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Biomedical Engineering College of Medicine Southwest Jiaotong University  Chengdu 610031 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