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The primary treatment for CNV involves intravitreal injections of anti\u2010vascular endothelial growth factor antibodies. Nevertheless, this approach still faces numerous limitations like poor patient compliance, high therapy expenditure and lack of response in some individuals. Herein, a series of anti\u2010neovascularization prodrugs, SU5402 (SU), modified with lipids of varying chain lengths (C12, C16, C20, C24, C28) is synthesized (SU\u2010C12, SU\u2010C16, SU\u2010C20, SU\u2010C24, SU\u2010C28). 1% polyvinyl alcohol (PVA) is used as a stabilizer to create nanoformulations of five prodrugs named SU\u2010C12 NPs, SU\u2010C16 NPs, SU\u2010C20 NPs, SU\u2010C24 NPs, SU\u2010C28 NPs. Among these, SU\u2010C20 NPs significantly prolong the retention of bioactive drug in the eye for up to 70 d. Moreover, SU\u2010C20 NPs demonstrate superior tissue permeability via enhanced cellular endocytosis and exocytosis. With its prolonged retention and improved penetration, SU\u2010C20 NPs reduce the fluorescence intensity of fundus leakage by 42.5% and the fluorescence area by 51.5% in CNV mice after four weeks, effectively inhibiting the progression of CNV. Altogether, small molecule drug SU is innovatively modified to improve its effectiveness for treating fundus neovascular diseases, proposing an alternative therapy for wet age\u2010related macular degeneration (wAMD).<\/jats:p>","DOI":"10.1002\/adma.202419263","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T02:20:51Z","timestamp":1738549251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Optimized Lipid\u2010Modified Prodrug for CNV Treatment"],"prefix":"10.1002","volume":"37","author":[{"given":"Xinying","family":"Lv","sequence":"first","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon\u2010Based Functional Materials &amp; Devices Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Shen","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon\u2010Based Functional Materials &amp; Devices Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwei","family":"Du","sequence":"additional","affiliation":[{"name":"School of Pharmacy Southwest Medical University  Luzhou 646000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyu","family":"Yue","sequence":"additional","affiliation":[{"name":"School of Pharmacy Southwest Medical University  Luzhou 646000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Tongji University  Shanghai 201804 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwan","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon\u2010Based Functional Materials &amp; Devices Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Miao","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon\u2010Based Functional Materials &amp; Devices Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxin","family":"Ji","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon\u2010Based Functional Materials &amp; Devices Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfu","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon\u2010Based Functional Materials &amp; Devices Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimou","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Pharmacy Southwest Medical University  Luzhou 646000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Tongji University  Shanghai 201804 China"},{"name":"Department of Thoracic Surgery Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"},{"name":"Central Laboratory Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1487-5479","authenticated-orcid":false,"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon\u2010Based Functional Materials &amp; Devices Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,2]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.26074"},{"key":"e_1_2_8_2_1","volume":"18","author":"Chang W.","year":"2024","journal-title":"ACS Nano"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27935-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.028"},{"key":"e_1_2_8_5_1","first-page":"820","volume":"14","author":"Crunkhorn S.","year":"2015","journal-title":"Nat. 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