{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T10:45:36Z","timestamp":1763117136813,"version":"3.45.0"},"reference-count":53,"publisher":"Wiley","issue":"29","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301217","81730025"],"award-info":[{"award-number":["82301217","81730025"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["82020108006"],"award-info":[{"award-number":["82020108006"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Retinal pigment epithelium (RPE) degeneration is the pathological hallmark of multifactorial dry age\u2010related macular degeneration (dAMD). Mounting evidence implicates oxidative stress and aberrant activation of mammalian target of rapamycin (mTOR) as key drivers of this process. Recent studies have shown that simultaneous modulation of these pathways may offer therapeutic benefit. However, clinical trials of rapamycin, an mTOR inhibitor widely employed in retinal research, have demonstrated limited efficacy, potentially due to poor bioavailability and paradoxical effects on RPE and photoreceptors. To overcome these challenges, APMNP@Rapa, a rapamycin\u2010loaded, methionine\u2010based ROS\u2010responsive polymeric micellar system functionalized with an Ab peptide for active targeting of damaged RPE is developed. The micelles self\u2010assemble from poly(ethylene glycol) \u2010 poly\u2010methionine copolymers,\u00a0leveraging methionine's endogenous nature and innate biocompatibility as an innovative ROS\u2010responsive motif. This design yields particles with exceptional circulation stability and enhanced biocompatibility. In the high\u2010ROS microenvironment of diseased RPE, APMNP@Rapa triggers on\u2010demand rapamycin release. In a sodium iodate (NaIO\n                    <jats:sub>3<\/jats:sub>\n                    )\u2010induced RPE oxidative stress model, APMNP@Rapa simultaneously inhibited aberrant mTOR activation, attenuated oxidative damage, and suppressed inflammatory response. These combined effects resulted in a marked preservation of the retina against degradation. Overall, the research establishes a paradigm for intravenous treatment of dAMD using multifunctional nanotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202502925","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:51:24Z","timestamp":1755600684000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intravenous Multifunctional Nanotherapy for Treating Dry Age\u2010Related Macular Degeneration"],"prefix":"10.1002","volume":"14","author":[{"given":"Xinyi","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye &amp; ENT Hospital of Fudan University  Shanghai 200031 China"},{"name":"Key laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences  Shanghai 200031 China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai 200031 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyi","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye &amp; ENT Hospital of Fudan University  Shanghai 200031 China"},{"name":"Key laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences  Shanghai 200031 China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai 200031 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Smart Drug Delivery (Ministry of Education) Minhang Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science School of Pharmacy Fudan University  Shanghai 201203 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye &amp; ENT Hospital of Fudan University  Shanghai 200031 China"},{"name":"Key laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences  Shanghai 200031 China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai 200031 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Smart Drug Delivery (Ministry of Education) Minhang Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science School of Pharmacy Fudan University  Shanghai 201203 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peixin","family":"Liu","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Division School of Pharmacy University of Wisconsin\u2010Madison  Madison Wisconsin 53705 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Smart Drug Delivery (Ministry of Education) Minhang Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science School of Pharmacy Fudan University  Shanghai 201203 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye &amp; ENT Hospital of Fudan University  Shanghai 200031 China"},{"name":"Key laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences  Shanghai 200031 China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai 200031 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiai","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye &amp; ENT Hospital of Fudan University  Shanghai 200031 China"},{"name":"Key laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences  Shanghai 200031 China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai 200031 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye &amp; ENT Hospital of Fudan University  Shanghai 200031 China"},{"name":"Key laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences  Shanghai 200031 China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai 200031 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye &amp; ENT Hospital of Fudan University  Shanghai 200031 China"},{"name":"Key laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences  Shanghai 200031 China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai 200031 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Smart Drug Delivery (Ministry of Education) Minhang Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science School of Pharmacy Fudan University  Shanghai 201203 China"},{"name":"Quzhou Fudan Institute  Quzhou 324003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Smart Drug Delivery (Ministry of Education) Minhang Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science School of Pharmacy Fudan University  Shanghai 201203 China"},{"name":"Department of Digestive Diseases National Regional Medical Center Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou 350212 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0483-945X","authenticated-orcid":false,"given":"Chen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye &amp; ENT Hospital of Fudan University  Shanghai 200031 China"},{"name":"Key laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences  Shanghai 200031 China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai 200031 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30488-5"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02609-5"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2004"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2020.08.027"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01520-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.26074"},{"key":"e_1_2_8_7_1","volume":"6","author":"Tzoumas N.","year":"2023","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2024.6490"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2024.02.021"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1709"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.03.002"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1994.1254"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2015.09.002"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222551899"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0172"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.119.10.1417"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2024.07.014"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11071304"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44303"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.26281"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000612R"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.36184"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0794-4"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101552"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10121944"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2207489119"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-15877"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2017.08.015"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79766"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201600292"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2018.11.001"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.09.009"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9101013"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.08.026"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2011.02.011"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202100746"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201801586"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16312-7"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.07.026"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-021-00858-8"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15144"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.01.036"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0913"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0404"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2005.10.005"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2013-0578"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddiscovery.2016.54"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/smtd.202100848"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202401613"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-010-0248-6"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.120591"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.06.003"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2012.10.013"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202502925","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T10:38:03Z","timestamp":1763116683000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202502925"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,19]]},"references-count":53,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/adhm.202502925"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202502925","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"type":"print","value":"2192-2640"},{"type":"electronic","value":"2192-2659"}],"subject":[],"published":{"date-parts":[[2025,8,19]]},"assertion":[{"value":"2025-06-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02925"}}