{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:03:40Z","timestamp":1790006620866,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"53","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"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":["82474086"],"award-info":[{"award-number":["82474086"]}],"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":["82173980"],"award-info":[{"award-number":["82173980"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Wet age\u2010related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), faces a clinical challenge of diminishing efficacy during long\u2010term anti\u2010VEGF monotherapy. An AI\u2010assisted analytical framework pinpointed impaired retinal pigment epithelium (RPE) autophagy and a pro\u2010inflammatory microenvironment driven by retinal microglia\u2010recruited monocytes as co\u2010conspirators in CNV progression. To tackle these dual culprits, we developed an intravitreal injectable hydrogel (Rab&amp;BCL\u2010M@G) that co\u2010encapsulates ranibizumab (Rab) and a small\u2010sized baicalin\u2010loaded microemulsion (BCL\u2010M), enabling controlled and sustained co\u2010delivery of both agents to the retina for over 14 days. Guided by the AI\u2010identified targets, we demonstrated that baicalin promoted dysfunctional mitochondria clearance via the AKT2\u2010PGC\u20101\u03b1\u2010mediated autophagic flux and suppressed monocyte recruitment by disrupting microglial CCL4 signaling. This two\u2010pronged action ameliorated inflammation and angiogenesis, synergizing with Rab. In a laser\u2010induced wAMD mouse model, a single intravitreal injection of Rab&amp;BCL\u2010M@G sustainably reduced CNV area, promoted repair, restored autophagy, and diminished microglial infiltration. Crucially, subsequent wet\u2010lab validation confirmed a positive pathological correlation among defective autophagy, inflammation, and angiogenesis, thereby closing the loop from computational prediction to experimental verification and explaining suboptimal long\u2010term performance after Rab monotherapy. This study proposes a promising synergistic strategy, advancing wAMD therapy through precision delivery and AI\u2010informed mechanism discovery.<\/jats:p>","DOI":"10.1002\/smll.74813","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:27:37Z","timestamp":1785144457000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sustained Retinal Delivery of Baicalin and Ranibizumab Overcomes the Anti\u2010VEGF Monotherapy Dilemma in wAMD"],"prefix":"10.1002","volume":"22","author":[{"given":"Xi","family":"Jiang","sequence":"first","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengqi","family":"Yang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Gong","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfei","family":"Mou","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"An","sequence":"additional","affiliation":[{"name":"Shanghai Academy of Al for Science  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9065-2659","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8054-1445","authenticated-orcid":false,"given":"Xiaona","family":"Wang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0934-4796","authenticated-orcid":false,"given":"Zhenzhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Sun","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Academy of Al for Science  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglei","family":"Cao","sequence":"additional","affiliation":[{"name":"Shanghai Academy of Al for Science  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8814-7004","authenticated-orcid":false,"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory For Pharmacology and Safety Research of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-1865","authenticated-orcid":false,"given":"Ding","family":"Qu","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010021\u201000265\u20102"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.26074"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c04494"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.09.036"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.120900"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120188"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202515852"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201011262\u20101"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2020.100858"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/exp.20230089"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c16196"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123828"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbaf040"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101353"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.49890"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201037025\u20107"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adi6626"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202400747"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3459"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010319\u201017121\u20100_11"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.05.035"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010023\u201001829\u2010y"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105444"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010019\u20101474\u20108"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020\u2010025\u201001110\u20104"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006221\u20102"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010024\u201003434\u20104"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2025.12.030"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbae414"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202509456"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.11.011"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202303659"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celbio.2025.100074"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celbio.2025.100217"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2024.100947"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201025\u20100237"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c16161"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122650"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0207285"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.010036"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4870"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10566"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201050500\u2010z"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010021\u201000764\u20103"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010022\u201001005\u20102"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1109\/tpami.2026.3667397"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac328"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac043"}],"container-title":["Small"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.74813","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/smll.74813","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.74813","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:24:38Z","timestamp":1790004278000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smll.74813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":48,"journal-issue":{"issue":"53","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/smll.74813"],"URL":"https:\/\/doi.org\/10.1002\/smll.74813","archive":["Portico"],"relation":{},"ISSN":["1613-6810","1613-6829"],"issn-type":[{"value":"1613-6810","type":"print"},{"value":"1613-6829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"assertion":[{"value":"2026-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e74813"}}