{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:07:04Z","timestamp":1790172424389,"version":"4.1.0"},"reference-count":76,"publisher":"Wiley","issue":"48","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the inflamed substantia nigra, resulting in striatal dopamine (DA) depletion and severe motor dysfunction. Here, we report a chemically programmed, inflammation\u2010responsive prodrug nanoparticle (NP) system\u2014\u03b2\u2010glucans\u2013DA(OAc)\n                    <jats:sub>2<\/jats:sub>\n                    NPs\u2014that enables precise oral gut\u2010to\u2010brain delivery of DA into deep brain regions. In this design, the acetylated DA prodrug DA(OAc)\n                    <jats:sub>2<\/jats:sub>\n                    is conjugated to \u03b2\u2010glucans via a reactive oxygen species (ROS)\u2013cleavable thioketal linker, thereby preventing DA autooxidation, enhancing stability during transit, and ensuring selective activation at neuroinflammatory sites. Following oral administration in PD mice, the NPs are recognized by Dectin\u20101, internalized by intestinal macrophages, and trafficked through the lymphatic and systemic circulation to cross the blood\u2013brain barrier, ultimately homing specifically to the inflamed substantia nigra in the deep brain. Within this pathological niche, dual responsiveness to elevated ROS and enzymatic activity triggers controlled prodrug cleavage, sustained DA regeneration, and restoration of striatal DA via the nigrostriatal pathway, ultimately rescuing motor function. This inflammation\u2010guided, modular prodrug platform provides a noninvasive and precise strategy for dopaminergic therapy, underscoring its potential as a transformative approach for PD management.\n                  <\/jats:p>","DOI":"10.1002\/adma.74148","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:56:36Z","timestamp":1784375796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chemically Programmed Prodrug Nanoparticles for Precise Oral Dopamine Delivery to Deep Brain Regions in Parkinson's Disease"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0260-2087","authenticated-orcid":false,"given":"Cam\u2010Hoa","family":"Mac","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering National Tsing Hua University  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Wei","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering National Tsing Hua University  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Nhung","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering National Tsing Hua University  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui\u2010To","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Neurological Institute Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Institute of Brain Science National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010An","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering National Taiwan University  Taipei Taiwan"},{"name":"Brain Research Center National Tsing Hua University  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Hui","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering National Taiwan University  Taipei Taiwan"},{"name":"Brain Research Center National Tsing Hua University  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van Khanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering National Tsing Hua University  Hsinchu Taiwan"},{"name":"Faculty of Chemical and Food Technology Ho Chi Minh City University of Technology and Education  Ho Chi Minh City Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8325-5008","authenticated-orcid":false,"given":"Sheng\u2010Yao","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering National Tsing Hua University  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih\u2010Kai","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering National Tsing Hua University  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Department of Surgery Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8006-4028","authenticated-orcid":false,"given":"Mai Thanh Thi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry University of Science Vietnam National University\u2212Ho Chi Minh City  Ho Chi Minh City Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian Yao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering National Tsing Hua University  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2507-3551","authenticated-orcid":false,"given":"Yu\u2010Jung","family":"Lin","sequence":"additional","affiliation":[{"name":"Research Center for Applied Sciences Academia Sinica  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0789-5236","authenticated-orcid":false,"given":"Hsing\u2010Wen","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering National Tsing Hua University  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.22360"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)00218\u2010X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.03.005"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/scipharm86040043"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201811122"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010020\u201000769\u20107"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007583422634"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.06.026"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.03.013"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn506408v"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.08.035"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2023.143245"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2021.101328"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656561003598919"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035\u2010015\u20100042\u20100"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.618411"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mattod.2017.05.006"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201029474\u20103"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10071"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104792"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/35072550"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462\u20105822.2005.00505.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20108722\u20102\u201025"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1FO02832D"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lwt.2025.117939"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.133124"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20069745"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201703674"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4NP00106K"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00213a044"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202401570"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010022\u201000684\u20106"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.6.3893"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102250"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202208316"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1385\/MN:27:2:163"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.16251"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2020.03.021"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42247\u2010019\u201000037\u20105"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471\u20104159.2002.00802.x"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202100701"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201043870\u20103"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2020.12.022"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar2003336"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.7150\/ntno.55165"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201012715\u20103"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/VIW.20230087"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.10.009"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.812148"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR\u2010D\u201023\u201001508"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c08473"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202300758"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13751"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00282"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201062478\u20103"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531\u2010024\u201000735\u2010w"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00152"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20108703(72)90204\u20109"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050010"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870100507"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25021131"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202105711"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202106723"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202201406"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.2c00741"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c09752"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531\u2010025\u201001098\u20106"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2025.105796"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600770703"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba3967"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.3390\/catal3040954"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c16367"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2023.146614"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.0c00019"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.93212.4"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010024\u201002533\u20104"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.74148","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.74148","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.74148","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:45:07Z","timestamp":1790171107000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.74148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,18]]},"references-count":76,"journal-issue":{"issue":"48","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/adma.74148"],"URL":"https:\/\/doi.org\/10.1002\/adma.74148","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,18]]},"assertion":[{"value":"2026-03-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e74148"}}