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Rapid Commun."],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Artemisinin derivatives (ARTs) induce ferrous iron\u2010dependent cell death (ferroptosis) by generating free radicals. Since the concentration of ferrous ions within cancer cells is high, the specific delivery of ARTs into cancer cells is advantageous for cancer therapy. Herein, we fabricate the biocompatible sulfobetaine polymer\u2010ARTs conjugates through the mechanochemical solid\u2010state copolymerization of sulfobetaine methacrylate (SBMA) and ARTs\u2010conjugated monomer. A polymer conversion rate of more than 90% is achieved within 60 min of copolymerization. The number average molecular weight and heterogeneity of resulting water\u2010soluble PSBMA\u2010ARTs conjugates are 8,000 g mol\n                    <jats:sup>\u22121<\/jats:sup>\n                    and 1.10, respectively. The progressive changes in ESR spectrum intensity with DMPO as a spin trapping agent reveal that the PSBMA\u2010ARTs conjugates ferrous ion\u2010dependently produce free radicals. The PSBMA\u2010ARTs conjugates indicate the cytotoxic activities against human hepatoblastoma cell lines, and the IC\n                    <jats:sub>50<\/jats:sub>\n                    of artesunate and PSBMA\u2010ARTs conjugates are 136 and 211 \u00b5\n                    <jats:sc>M<\/jats:sc>\n                    , respectively. Furthermore, it is demonstrated that PSBMA\u2010ARTs conjugates internalized into cells generate the free radicals and induce the lipid peroxidation in cell membranes or intracellularly involved in ferroptosis, determined by the live\u2010cell imaging with C11\u2010BODIPY. This novel drug carrier, which does not require drug release, is a promising cancer ferroptosis inducer for expanding pharmaceutical treatment strategies.\n                  <\/jats:p>","DOI":"10.1002\/marc.70341","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:28:15Z","timestamp":1782188895000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biocompatible Sulfobetaine Polymer\u2010Artemisinin Conjugates Inducing Ferroptosis in Cancer Cells: Synthesis by Mechanochemical Solid\u2010State Polymerization and Characterization"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9773-1429","authenticated-orcid":false,"given":"Naoki","family":"Doi","sequence":"first","affiliation":[{"name":"Laboratory of Pharmaceutical Physical Chemistry Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukinori","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Physical Chemistry College of Pharmaceutical Sciences Matsuyama University  Matsuyama Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Sasai","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Gifu University of Medical Science  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Nagai","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Physical Chemistry Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Koike","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Physical Chemistry Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madoka","family":"Ikawa","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Physical Chemistry Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Physical Chemistry Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Physical Chemistry Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Kuzuya","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Physical Chemistry Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4222-0004","authenticated-orcid":false,"given":"Shin\u2010ichi","family":"Kondo","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Physical Chemistry Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"6387","article-title":"A New Concept for Macromolecular Therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent Smancs","volume":"46","author":"Matsumura Y.","year":"1986","journal-title":"Cancer 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