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Inspired by this principle, chiral nanoparticles have emerged as promising candidates for immunomodulation in inflammation\u2010related diseases. However, whether and how their chiral cues regulate extracellular matrix (ECM) remodeling remains largely unexplored. Herein, we report the design of L\u2010cysteine\u2010configured polyurethane nanoparticles (L\u2010CN) through covalent grafting of naturally chiral L\u2010cysteine, and demonstrate their therapeutic potential for ectopia lentis (EL) \u2014 a disease characterized by progressive zonular fiber degeneration. Mechanistically, L\u2010CN suppresses the nuclear factor kappa B signaling pathway in M\n                    <jats:sub>1<\/jats:sub>\n                    macrophages through the anti\u2010inflammatory activity of L\u2010cysteine, thereby attenuating inflammatory responses and reducing ECM degradation in vitro. In an EL rat model, it facilitates CD163\n                    <jats:sup>+<\/jats:sup>\n                    M\n                    <jats:sub>2<\/jats:sub>\n                    macrophages polarization, leading to the restoration of FBN1 and MFAP2 expression in zonular fibers and ultimately promoting zonular fiber reconstruction. Overall, this study establishes a chirality\u2010mediated immunomodulatory strategy for ECM reconstruction and provides a minimally invasive therapeutic approach for EL and potentially other matrix\u2010degenerative disorders.\n                  <\/jats:p>","DOI":"10.1002\/advs.202522741","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T12:00:47Z","timestamp":1785153647000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chiral Nanoparticles Suppress Inflammatory Infiltration to Promote Extracellular Matrix Remodeling for Ectopia Lentis Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Yinuo","family":"Wen","sequence":"first","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye &amp; ENT Hospital Fudan University  Shanghai China"},{"name":"Key Laboratory of Myopia and Related Eye Diseases, NHC; Key Laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai China"},{"name":"Shanghai Medical College (SHMC) Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hong Kong Joint Laboratory for Water Security Beijing Normal University  Zhuhai China"},{"name":"Center For Water Research Advanced Institute of Natural Sciences Beijing Normal University  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Department of Orthopedic Surgery Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye &amp; 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