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The neurokinin 1 receptor (NK1R) is a target for controlling T helper 17 (Th17) and regulatory T cell (Treg) imbalances. This work creates a silk fibroin (SF) nanoparticle hydrogel that targets NK1R with CP\u201099,994 (CP). Combining CP and SF to generate stable nanoparticles while integrating a flexible hydrogel material results in a sustained\u2010release ophthalmic drop formulation (SF@CP@Gel), which provides a long\u2010lasting ocular formulation with anti\u2010inflammatory and reparative properties. SF@CP@Gel could maintain a stable CP concentration for 25 h with detectable biological activity. The cell counting kit\u20108 and 2,7\u2010DHL\u2010DA results reveal that SF@CP@Gel has no cytotoxic effect on human corneal epithelial cells (HCECs) and decreases the reactive oxygen species level in oxidatively damaged HCECs. Cell scratch assays demonstrate that SF@CP@Gel can greatly increase HCEC migration and proliferation within 24 h. Furthermore, in vivo therapy with topical SF@CP@Gel twice daily markedly reduce clinical symptoms by reducing the amount of pathogenic Th17 cells while efficiently restoring Treg activity. In summary, this work reveals that SF@CP@Gel might attenuate DED by inhibiting NK1R\u2010mediated SP signaling and thereby modulating the Th17\/Treg ratio, a potential anti\u2010inflammatory and repair treatment method for DED.<\/jats:p>","DOI":"10.1002\/advs.202404835","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T03:25:42Z","timestamp":1740194742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Silk Fibroin Nanoparticle Hydrogel Loaded With NK1R Antagonist Has Synergistic Anti\u2010Inflammatory and Reparative Effects on Dry Eye Disease"],"prefix":"10.1002","volume":"12","author":[{"given":"Bo","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 610000 China"},{"name":"Human Disease Genes Key Laboratory of Sichuan Province and Institute of Laboratory Medicine Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 610000 China"},{"name":"Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026) Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 610000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1299-1908","authenticated-orcid":false,"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Deyang People's Hospital  Deyang 618000 China"},{"name":"School of Medicine University of Electronic Science and Technology of China  Chengdu 610000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 610000 China"},{"name":"Department of Ophthalmology Deyang People's Hospital  Deyang 618000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueming","family":"Ju","sequence":"additional","affiliation":[{"name":"Human Disease Genes Key Laboratory of Sichuan Province and Institute of Laboratory Medicine Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 610000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 610000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 610000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 610000 China"},{"name":"Human Disease Genes Key Laboratory of Sichuan Province and Institute of Laboratory Medicine Sichuan Academy of Medical Sciences &amp; 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Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 610000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialing","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 610000 China"},{"name":"School of Medicine University of Electronic Science and Technology of China  Chengdu 610000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 610000 China"},{"name":"School of Medicine University of Electronic Science and Technology of China  Chengdu 610000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Chai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology\u2010Head and Neck Surgery Zhongda Hospital School of Life Sciences and Technology School of Medicine, Advanced Institute for Life and Health Jiangsu Province High\u2010Tech Key Laboratory for Bio\u2010Medical Research Southeast University  Nanjing 210096 China"},{"name":"Co\u2010Innovation Center of Neuroregeneration Nantong University  Nantong 226001 China"},{"name":"Department of Neurology Aerospace Center Hospital School of Life Science Beijing Institute of Technology  Beijing 100081 China"},{"name":"Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  Chengdu 610072 China"},{"name":"Southeast University Shenzhen Research Institute  Shenzhen 518063 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Sichuan Academy of Medical Sciences &amp; 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