{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:21:13Z","timestamp":1791555673000,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T00:00:00Z","timestamp":1642896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81827804"],"award-info":[{"award-number":["81827804"]}],"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":["81800540"],"award-info":[{"award-number":["81800540"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gallbladder cancer (GBC) is a rare but the most malignant type of biliary tract tumor. It is usually diagnosed at an advanced stage and conventional treatments are unsatisfactory. As a proteasome inhibitor, bortezomib (BTZ) exhibits excellent antitumor ability in GBC. However, the long\u2010term treatment efficacy is limited by its resistance, poor stability, and high toxicity. Herein, BTZ\u2010encapsulated pH\u2010responsive copolymeric nanoparticles with estrone (ES\u2010NP<jats:sub>(BTZ; Ce6)<\/jats:sub>) for GBC\u2010specific targeted therapy is reported. Due to the high estrogen receptor expression in GBC, ES\u2010NP<jats:sub>(BTZ; Ce6)<\/jats:sub> can rapidly enter the cells and accumulate near the nucleus via ES\u2010mediated endocytosis. Under acidic tumor microenvironment (TME) and 808\u00a0nm laser irradiation, BTZ is released and ROS is generated by Ce6 to destroy the \u201cbounce\u2010back\u201d response pathway proteins, such as DDI2 and p97, which can effectively inhibit proteasomes and increase apoptosis. Compared to the traditional treatment using BTZ monotherapy, ES\u2010NP<jats:sub>(BTZ; Ce6)<\/jats:sub> can significantly impede disease progression at lower BTZ concentrations and improve its resistance. Moreover, ES\u2010NP<jats:sub>(BTZ; Ce6)<\/jats:sub> demonstrates similar antitumor abilities in patient\u2010derived xenograft animal models and five other types of solid tumor cells, revealing its potential as a broad\u2010spectrum antitumor formulation.<\/jats:p>","DOI":"10.1002\/advs.202103895","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T02:33:41Z","timestamp":1642991621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Bortezomib\u2010Encapsulated Dual Responsive Copolymeric Nanoparticles for Gallbladder Cancer Targeted Therapy"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5113-754X","authenticated-orcid":false,"given":"Mingyu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"},{"name":"School of Medicine Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1449-5564","authenticated-orcid":false,"given":"Sarun","family":"Juengpanich","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"},{"name":"School of Medicine Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7583-4523","authenticated-orcid":false,"given":"Shijie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"},{"name":"School of Medicine Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-1920","authenticated-orcid":false,"given":"Win","family":"Topatana","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"},{"name":"School of Medicine Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8209-3188","authenticated-orcid":false,"given":"Ziyi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"},{"name":"College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiasheng","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Physical and Mathematical Sciences Nanyang Technological University  Singapore 637371 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidan","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry Zhejiang University  Hangzhou 310027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5015-7370","authenticated-orcid":false,"given":"Sukanda","family":"Jiansirisomboon","sequence":"additional","affiliation":[{"name":"School of Ceramic Engineering Institute of Engineering Suranaree University of Technology  Nakhon Ratchasima 30000 Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2947-4456","authenticated-orcid":false,"given":"Zhen","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"},{"name":"College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-3743","authenticated-orcid":false,"given":"Suparat","family":"Tongpeng","sequence":"additional","affiliation":[{"name":"School of Ceramic Engineering Institute of Engineering Suranaree University of Technology  Nakhon Ratchasima 30000 Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6457-0577","authenticated-orcid":false,"given":"Xiujun","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University  Hangzhou 310016 China"},{"name":"School of Medicine Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,23]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.51.6.349"},{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1429"},{"key":"e_1_2_7_1_3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.11815"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(03)01021-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.537789"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.152"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00324-2"},{"key":"e_1_2_7_4_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2020.11.016"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.117.015370"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3321"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.57.042905.122625"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E20-04-0238"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.05.035"},{"key":"e_1_2_7_7_3","first-page":"5,","author":"Koizumi S.","year":"2016","journal-title":"eLife"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr0502504"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.23.8220"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.66.0662"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.05.009"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2018.06.014"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14851"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6CS00592F"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.6b05910"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3110"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201605897"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr5004198"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.08.003"},{"key":"e_1_2_7_14_3","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.9b02904"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2803"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2018.06.014"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CC04656F"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201806957"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201505869"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.08.025"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201802808"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay0152"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201700448"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b01424"},{"key":"e_1_2_7_23_3","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201801507"},{"key":"e_1_2_7_23_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.10.048"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-019-0566-2"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.0c00047"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S298146"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b04181"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202103895","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202103895","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202103895","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T18:36:30Z","timestamp":1759775790000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202103895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,23]]},"references-count":43,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1002\/advs.202103895"],"URL":"https:\/\/doi.org\/10.1002\/advs.202103895","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,23]]},"assertion":[{"value":"2021-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2103895"}}