{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:16:50Z","timestamp":1784891810018,"version":"3.55.0"},"reference-count":66,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The advent of biomacromolecules antagonizing vascular endothelial growth factor (VEGF) has revolutionized the treatment of neovascular age\u2010related macular degeneration (nAMD). However, frequent intravitreal injections of these biomacromolecules impose an enormous burden on patients and create a massive workload for healthcare providers. This causes patients to abandon therapy, ultimately leading to progressive and irreversible vision loss. In order to address this unmet clinical need, a noninvasive treatment for nAMD is developed. An optimized cell\u2010penetrating peptide derivative,\n                    <jats:sup>bxy<\/jats:sup>\n                    Penetratin (bxyWP), is used to non\u2010covalently complex with the anti\u2010VEGF protein aflibercept (AFL) via reversible hydrophobic interaction. The interaction is crucial for AFL delivery, neither impairing the affinity of AFL to pathological VEGF, nor being interfered by endogenous proteins in tear fluids. AFL\/bxyWP eye drops exhibit prolonged retention on the eye and excellent absorption into the posterior ocular segment following topical administration, with significant drug distribution to the retina and choroid. In a laser\u2010induced choroidal neovascularization model on cynomolgus monkeys, AFL\/bxyWP eye drops efficiently reduce lesion size and leakage comparable to conventional intravitreal injection of AFL. These results suggest that AFL\/bxyWP eye drops are feasible self\u2010administered treatment for neovascular retinal diseases and potentially become a substitute for intravitreal injections.\n                  <\/jats:p>","DOI":"10.1002\/advs.202410744","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T14:49:31Z","timestamp":1738248571000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Peptide\u2010Bound Aflibercept Eye Drops for Treatment of Neovascular Age\u2010Related Macular Degeneration in Nonhuman Primates"],"prefix":"10.1002","volume":"12","author":[{"given":"Xingyan","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Fudan University &amp; Key Laboratory of Smart Drug Delivery (Fudan University) Ministry of Education  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye and ENT Hospital Fudan University  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Alephoson Biopharmaceuticals Limited  Hong Kong SAR 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin TK","family":"Lee","sequence":"additional","affiliation":[{"name":"Alephoson Biopharmaceuticals Limited  Hong Kong SAR 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyang","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Fudan University &amp; Key Laboratory of Smart Drug Delivery (Fudan University) Ministry of Education  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marten E","family":"Brelen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences The Chinese University of Hong Kong  Hong Kong SAR 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyue","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Fudan University &amp; Key Laboratory of Smart Drug Delivery (Fudan University) Ministry of Education  Shanghai 201203 China"},{"name":"Quzhou Fudan Institute  Quzhou 324003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9600-0982","authenticated-orcid":false,"given":"Gang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Fudan University &amp; Key Laboratory of Smart Drug Delivery (Fudan University) Ministry of Education  Shanghai 201203 China"},{"name":"Quzhou Fudan Institute  Quzhou 324003 China"},{"name":"Shanghai Engineering Research Center of ImmunoTherapeutics  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2102061"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.26074"},{"key":"e_1_2_10_3_1","unstructured":"WHO World report on vision https:\/\/www.who.int\/publications\/i\/item\/9789241516570(accessed: October2019)."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(13)70145-1"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2007.03.008"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.30344"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2021.0221"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2017.03.057"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00010-1"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101072"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2017-311258"},{"key":"e_1_2_10_12_1","first-page":"353","volume":"101","author":"Wecker T.","year":"2017","journal-title":"Br. 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