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Effective pharmacotherapy remains elusive, due to the restrictive blood\u2010spinal cord barrier (BSCB), underscoring the urgent need for targeted and efficient drug delivery strategies. Luteolin (LUT), a natural flavonoid with potent anti\u2010neuroinflammatory properties, presents a promising therapeutic option; however, it is compromised by poor solubility, low bioavailability, and limited BSCB penetration. Drawing inspiration from the traditional Chinese medicine concept of the \u201corifice\u2010opening\u201d effect of borneol (BO), we developed BO\u2010modified mesoporous silica nanoparticles (MSN\u2010BO@LUT) for targeted LUT delivery to the spinal cord. MSN\u2010BO@LUT significantly enhanced LUT delivery to the spinal cord, achieving a 286.36\u2010fold increase over LUT, and maintained a concentration of 802.17 ng\/mL at 24\u00a0h. MSN\u2010BO@LUT demonstrated robust anti\u2010neuroinflammatory and neuroprotective effects in SCI mice, reducing microglial infiltration, promoting functional recovery, and showing favorable efficacy and safety compared with the positive control methylprednisolone. Mechanistically, released LUT targets protein arginine N\u2010methyltransferase, reduces toll\u2010like receptor 4 methylation, and inhibits nuclear factor kappa B\u2010mediated pro\u2010inflammatory signaling, thereby suppressing microglial M1 polarization. These findings suggest that MSN\u2010BO@LUT not only provides a developed, safe, effective nanotherapeutic strategy for SCI treatment but also serves as a translatable template for developing precision nanomedicines targeting CNS disorders.<\/jats:p>","DOI":"10.1002\/advs.77460","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A BSCB\u2010Penetrating Nanoplatform for Enhanced Luteolin Delivery in PRMT2\u2010Targeted Epigenetic Therapy of Spinal Cord Injury"],"prefix":"10.1002","author":[{"given":"Yixuan","family":"Wang","sequence":"first","affiliation":[{"name":"Spine Disease Institute Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education Shanghai University of Traditional 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