{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:34:46Z","timestamp":1790886886745,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"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":["22474042"],"award-info":[{"award-number":["22474042"]}],"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":["82203041"],"award-info":[{"award-number":["82203041"]}],"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":["U22A20328"],"award-info":[{"award-number":["U22A20328"]}],"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":["W2412035NSFC\u2010FWO"],"award-info":[{"award-number":["W2412035NSFC\u2010FWO"]}],"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":["23490712700"],"award-info":[{"award-number":["23490712700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["20430711800"],"award-info":[{"award-number":["20430711800"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["23ZR1475000"],"award-info":[{"award-number":["23ZR1475000"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Glioblastoma (GBM) is the most aggressive subtype of primary brain tumors, which marginally respond\u00a0to standard chemotherapy due to the blood\u2010brain barrier (BBB) and the low tumor specificity of the therapeutics. Herein, a double\u2010layered microneedle (MN) patch is rationally engineered by integrating acid and light dual\u2010activatable PROteolysis TArgeting Chimera (PROTAC) nanoparticles and self\u2010oxygenating BSA\u2010MnO\n                    <jats:sub>2<\/jats:sub>\n                    (BM) nanoparticles for GBM treatment. The MN is administrated at the tumor site to locally deliver the PROTAC prodrug and BM nanoparticles. The PROTAC nanoparticles are rapidly released from the outer layer of the MN and specifically activated in the acidic intracellular environment of tumor cells. Subsequently, near\u2010infrared light activates the photosensitizer to produce singlet oxygen (\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) through photodynamic therapy (PDT), thereby triggering spatiotemporally\u2010tunable degradation of bromodomain and extraterminal protein 4 (BRD4). The BM nanoparticles, in the inner layer of the MN, serve as an oxygen supply station, and counteracts tumor hypoxia by converting hydrogen peroxide\u00a0(H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) into oxygen (O\n                    <jats:sub>2<\/jats:sub>\n                    ), thus promoting PDT and PROTAC activation. This PROTAC prodrug\u2010integrated MN significantly inhibits tumor growth in both subcutaneous and orthotopic GBM tumor models. This study describes the first spatiotemporally\u2010tunable protein degradation strategy for highly efficient GBM therapy, potentially advancing precise therapy of other kinds of refractory brain tumors.\n                  <\/jats:p>","DOI":"10.1002\/adma.202411869","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T09:36:23Z","timestamp":1741685783000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Self\u2010Oxygenating PROTAC Microneedle for Spatiotemporally\u2010Confined Protein Degradation and Enhanced Glioblastoma Therapy"],"prefix":"10.1002","volume":"37","author":[{"given":"Xingyu","family":"Jiang","sequence":"first","affiliation":[{"name":"School of Chemistry and Molecular Engineering East China Normal University  Shanghai 200241 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Biology and Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzheng","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200011 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfang","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjue","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Biology and Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Biology and Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Biology and Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Biology and Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Engineering East China Normal University  Shanghai 200241 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Biology and Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University  Beijing 100070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zan","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200011 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Ping","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Health Technology and Engineering and Institute of Systems and Physical Biology Shenzhen Bay Laboratory  Shenzhen 518067 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijun","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemical Biology and Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"School of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4391-2507","authenticated-orcid":false,"given":"Zhiai","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Engineering East China Normal University  Shanghai 200241 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00250-4"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05520-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00516-y"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21613"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.0023"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105780"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.18718"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-2182"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3643"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4185"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05788-y"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202103978"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202307454"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2397"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3958"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2017148118"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1424220112"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1712363115"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0916-y"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.03.003"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00885-3"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00736-3"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00193D"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3CS00100H"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00200K"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2023.04.028"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202314132"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-024-01266-z"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202107347"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CS00762A"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32050-4"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2018.11.006"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b06422"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c10177"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50735-w"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.31635\/ccschem.022.202101529"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00771"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c05499"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202101155"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c01929"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5b05043"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1917891117"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c03252"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwab172"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aan5692"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0598-9"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.08.009"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202106606"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matt.2021.11.017"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe2620"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba7260"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vesic.2022.100014"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c06462"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2021.118168"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2016897118"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41378-019-0088-8"},{"key":"e_1_2_8_58_1","volume":"33","author":"Lee Y.","year":"2021","journal-title":"Adv. Mater."},{"key":"e_1_2_8_59_1","first-page":"584","volume":"37","author":"Chauvet D.","year":"2016","journal-title":"Ultraschall Med."},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14446-2"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2210418120"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202411869","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.202411869","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202411869","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T10:49:22Z","timestamp":1775645362000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.202411869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,3]]},"references-count":61,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/adma.202411869"],"URL":"https:\/\/doi.org\/10.1002\/adma.202411869","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,3]]},"assertion":[{"value":"2024-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2411869"}}