{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:24:49Z","timestamp":1787055889403,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2026A1515011519"],"award-info":[{"award-number":["2026A1515011519"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Therapeutic relapse driven by bortezomib resistance represents a formidable clinical barrier in the management of multiple myeloma (MM). Here, a carrier\u2010free, supramolecular nanoplatform was engineered through the spontaneous co\u2010assembly of two natural alkaloids, berberine (BBR) and nitidine chloride (NC), termed BBR\/NC\u2010SAPs, to counter this malignancy. Driven by cooperative \u03c0\u2010\u03c0 stacking and van der Waals forces, BBR\/NC\u2010SAPs display superior anti\u2010MM efficacy and optimized biosafety as compared to the free\u2010drug combination. Quantitative proteomics and functional landscapes showed that BBR\/NC\u2010SAPs robustly activate iron\u2010dependent ferroptosis, as evidenced by massive lipid peroxidation, intracellular Fe\n                    <jats:sup>2+<\/jats:sup>\n                    overload, and mitochondrial depolarization. Mechanistically, integrated target deconvolution and atomistic molecular modeling identified NR2F2 as a direct target of BBR\/NC\u2010SAPs. Functional knock\u2010out and rescue evaluations definitively validated that NR2F2 is an essential mediator governing the therapeutic response, as NR2F2 depletion occluded the ferroptotic cascade, and lentiviral reconstitution fully restored cellular sensitivity and GPX4\u2010associated ferroptosis activation. Further, BBR\/NC\u2010SAPs markedly suppressed tumor growth and prolonged survival in bortezomib\u2010resistant MM xenograft models, a therapeutic benefit actively reversed by the ferroptosis inhibitor ferrostatin\u20101. Collectively, this work highlights a paradigm of natural product\u2010derived nanotechnology that targets the NR2F2\u2013GPX4 axis, offering a promising supramolecular strategy to overcome drug resistance in refractory hematological tumors.\n                  <\/jats:p>","DOI":"10.1002\/advs.77174","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T11:31:07Z","timestamp":1787052667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Carrier\u2010Free Berberine\/Nitidine Chloride Self\u2010Assembled Nanoparticles Induce Ferroptosis to Overcome Bortezomib Resistance in Multiple Myeloma"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9803-5820","authenticated-orcid":false,"given":"Yiwen","family":"Lv","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0541-0696","authenticated-orcid":false,"given":"Shuang","family":"Liu","sequence":"additional","affiliation":[{"name":"The Affiliated Guangdong Second Provincial General Hospital of Jinan University  Guangzhou Guangdong People's Republic of China"},{"name":"Key Laboratory of Regenerative Medicine of Ministry of Education  Guangzhou Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wu","sequence":"additional","affiliation":[{"name":"The Affiliated Guangdong Second Provincial General Hospital of Jinan University  Guangzhou Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiluan","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Guangdong Second Provincial General Hospital of Jinan University  Guangzhou Guangdong People's Republic of 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Jinan University  Guangzhou Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiming","family":"Ou","sequence":"additional","affiliation":[{"name":"The Affiliated Guangdong Second Provincial General Hospital of Jinan University  Guangzhou Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Shen","sequence":"additional","affiliation":[{"name":"The Affiliated Guangdong Second Provincial General Hospital of Jinan University  Guangzhou Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Liu","sequence":"additional","affiliation":[{"name":"The Affiliated Guangdong Second Provincial General Hospital of Jinan University  Guangzhou Guangdong People's Republic of 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