{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:59:16Z","timestamp":1792900756531,"version":"4.5.0"},"reference-count":66,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Low immunogenicity and highly immunosuppressive tumor microenvironment (TME) present major challenges in immunotherapy, as they restrict T lymphocyte infiltration and activation. Although ferroptosis induction has emerged as a promising approach for enhancing tumor immunogenicity and promoting T cell recruitment, its efficacy is frequently compromised by cholesterol\u2010driven T cell functional exhaustion. To address these limitations, we engineered tumor\u2010targeting, TME\u2010responsive, and size\u2010switchable supramolecular nanoprodrugs that enable multidimensional immune activation. Nanoprodrugs orchestrate a sophisticated cascade of immune activation through four synergistic mechanisms: 1) size\u2010switchable disassembly upon glutathione\/ cholesterol exposure for deep tumor penetration; 2) redox imbalance driven by reactive nitrogen species accumulation and glutathione depletion via the synergistic action of oxaliplatin, ferrocene, and RRx\u2010001 for ferroptosis augmentation; 3) immunogenic cell death induction via ferroptosis\u2010apoptosis to initiate tumor immunity cycle, promoting T cell infiltration; and 4) T cell function reinvigoration with the downregulation of programmed cell death protein 1 and T\u2010cell immunoglobulin 3 expression through cholesterol depletion in TME. This integrated approach achieved primary and distant tumor growth suppression, established durable immune memory against recurrence, and systemically enhanced the antitumor immunity. By concurrently targeting tumor immunogenicity, TME immunosuppression, and T cell exhaustion, this multidimensional strategy represents a transformative advancement in cancer immunotherapy.<\/jats:p>","DOI":"10.1002\/smll.202514467","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T11:47:02Z","timestamp":1771328822000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Size\u2010Transformable Supramolecular Nanoprodrugs Enable Redox Imbalance Amplification and Cholesterol Modulation to Boost Multidimensional Tumor Immunotherapy"],"prefix":"10.1002","volume":"22","author":[{"given":"Qi","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy Hebei Province Key Laboratory of Innovative Drug Research and Evaluation Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingfeng","family":"Meng","sequence":"additional","affiliation":[{"name":"The Fourth Affiliated Hospital of Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Fu","sequence":"additional","affiliation":[{"name":"Core Facilities and Centers Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luya","family":"Li","sequence":"additional","affiliation":[{"name":"The Fourth Affiliated Hospital of Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Core Facilities and Centers Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaxing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Core Facilities and Centers Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1282-2445","authenticated-orcid":false,"given":"Lina","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Hebei Province Key Laboratory of Innovative Drug Research and Evaluation Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010025\u201003495\u2010z"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.88"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.09.020"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010025\u201000832\u20109"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010022\u201001141\u20101"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2024.102817"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.70009"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.09.010"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202504684"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14356"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2025.216846"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202312500"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202307006"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202408502"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202514256"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202508753"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202506599"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202311733"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202415673"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202417422"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202518305"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202507864"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202303829"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202318155"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.supmat.2024.100066"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202314536"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202501271"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c02964"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201015591\u20104"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c09254"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.3c04813"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202417370"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202500491"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202208241"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202103721"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202002138"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.04.002"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c08622"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2025.2519066"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123559"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010021\u201000826\u20106"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.3c16213"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202412844"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c17428"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202405826"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202303567"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40843\u2010025\u20103348\u20101"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202312528"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202502581"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cclet.2024.109854"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202417518"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201057718\u20105"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408518"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202402809"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202006483"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20210111"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010024\u201001757\u20104"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.06.053"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp056751a"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00298a003"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar500055s"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.07.002"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202103015"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202108971"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c16329"}],"container-title":["Small"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202514467","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/smll.202514467","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202514467","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:16:11Z","timestamp":1783462571000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smll.202514467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,17]]},"references-count":66,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/smll.202514467"],"URL":"https:\/\/doi.org\/10.1002\/smll.202514467","archive":["Portico"],"relation":{},"ISSN":["1613-6810","1613-6829"],"issn-type":[{"value":"1613-6810","type":"print"},{"value":"1613-6829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,17]]},"assertion":[{"value":"2025-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14467"}}