{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:04:19Z","timestamp":1789499059568,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52503205"],"award-info":[{"award-number":["52503205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572387"],"award-info":[{"award-number":["82572387"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Age\u2010related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly, driven by oxidative stress, chronic inflammation, and pathological choroidal neovascularization (CNV). Although intravitreal anti\u2010vascular endothelial growth factor (VEGF) therapies remain the current clinical standard, their invasive nature and requirement for long\u2010term repeated injections present substantial risks and patient burden, underscoring an urgent need for noninvasive therapeutic alternatives. Here, we develop a noninvasive, cornea\u2010penetrating nanodrug based on chitosan\u2010modified lipid\u2010polymer hybrid nanoparticles (LPNPs) for co\u2010delivery of lutein and VEGF\u2010silencing siRNA (Chi@Lu\/si NPs) to treat AMD. The structurally stabilized nanoparticles overcome the intrinsic instability of siRNA and the poor solubility of lutein, while the chitosan coating confers strong mucoadhesion and transient modulation of epithelial tight junctions, enabling a 3.3\u2010fold enhancement in trans\u2010epithelial transport across the ocular surface. Once delivered to the posterior segment, lutein effectively scavenges excessive reactive oxygen species and suppresses inflammatory cascades, whereas siRNA\u2010VEGF achieves precise VEGF gene silencing, collectively interrupting the pathological cycle driving CNV progression. In a laser\u2010induced CNV mouse model, topical administration of Chi@Lu\/si NPs twice daily exerted potent inhibitory effects on neovascularization, with therapeutic efficacy comparable to that of\u00a0intravitreal bevacizumab, reducing CNV lesion thickness to 58.9% of pre\u2010treatment levels while maintaining excellent ocular biocompatibility.<\/jats:p>","DOI":"10.1002\/adma.74994","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:16:48Z","timestamp":1789496208000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cornea\u2010Penetrating Nanodrug Co\u2010Delivering VEGF\u2010Silencing siRNA and Lutein for Treating Age\u2010Related Macular Degeneration"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1158-4555","authenticated-orcid":false,"given":"Yong","family":"Li","sequence":"first","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; Liangzhu Laboratory, &amp; Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3429-5241","authenticated-orcid":false,"given":"Fan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; Liangzhu Laboratory, &amp; Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; Liangzhu Laboratory, &amp; Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; Liangzhu Laboratory, &amp; Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8803-7162","authenticated-orcid":false,"given":"Jinshi","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; Liangzhu Laboratory, &amp; Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5390-3233","authenticated-orcid":false,"given":"Yiquan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; Liangzhu Laboratory, &amp; Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxian","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; Liangzhu Laboratory, &amp; Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7728-7378","authenticated-orcid":false,"given":"Ning","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; Liangzhu Laboratory, &amp; Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyin","family":"Sheng","sequence":"additional","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; Liangzhu Laboratory, &amp; Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0936-2791","authenticated-orcid":false,"given":"Haijie","family":"Han","sequence":"additional","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; Liangzhu Laboratory, &amp; Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5107-8268","authenticated-orcid":false,"given":"Qiuli","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; Liangzhu Laboratory, &amp; Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0543-2465","authenticated-orcid":false,"given":"Shu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center For Nanomedicine and Department of Anesthesiology, Perioperative, and Pain Medicine Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4277-3728","authenticated-orcid":false,"given":"Wei","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6764-7365","authenticated-orcid":false,"given":"Ke","family":"Yao","sequence":"additional","affiliation":[{"name":"Key Lab of Ophthalmology Eye Center of The Second Affiliated Hospital, &amp; 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