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However, monometallic pyroptosis biotuners have not been explored until now. Here, we discover for the first time that biodegradable monometallic Al can act as a pyroptosis biotuner for tumor therapy. pH\u2010sensitive Al nanoparticles (Al@P) are obtained by equipping polyethylene glycol\u2010<jats:italic>b<\/jats:italic>\u2010(poly(methyl methacrylate)\u2010co\u2010poly(4\u2010vinylpyridine), which can exert their effect at the tumor site without affecting normal cells. The H<jats:sub>2<\/jats:sub> and Al<jats:sup>3+<\/jats:sup> release by Al@P in the acidic environment of tumors disrupts the redox balance and ionic homeostasis in tumor cells, thus generating large amounts of reactive oxygen species (ROS), leading to caspase\u20101 activation, gasdermin D cleavage, and IL\u20101\u03b2\/LDH release, which induces canonical pyroptotic death. Meanwhile, the prodrug Doxorubicin (Pro\u2010DOX) is successfully loaded onto Al@P (Al@P\u2010P) and can be activated by ROS to release DOX in the tumor cells, thus further improving the tumor\u2010killing efficiency. Ultimately, Al@P\u2010P is degradable and exhibits efficient tumor inhibition.<\/jats:p>","DOI":"10.1002\/anie.202317304","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T08:06:03Z","timestamp":1706774763000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Biodegradable Monometallic Aluminum as a Biotuner for Tumor Pyroptosis"],"prefix":"10.1002","volume":"63","author":[{"given":"Yuan","family":"Liang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Jilin, Changchun 130022 China"},{"name":"University of Science and Technology of China  Anhui, Hefei 230026 China"},{"name":"Ganjiang Innovation Academy Chinese Academy of Sciences  Jiangxi, Ganzhou 341000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengpeng","family":"Lei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Jilin, Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"An","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Jilin, Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengye","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Jilin, Changchun 130022 China"},{"name":"University of Science and Technology of China  Anhui, Hefei 230026 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Jilin, Changchun 130022 China"},{"name":"University of Science and Technology of China  Anhui, Hefei 230026 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Jilin, Changchun 130022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5433-8611","authenticated-orcid":false,"given":"Hongjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Jilin, Changchun 130022 China"},{"name":"University of Science and Technology of China  Anhui, Hefei 230026 China"},{"name":"Department of Chemistry Tsinghua University  Beijing 100084 China"},{"name":"Ganjiang Innovation Academy Chinese Academy of Sciences  Jiangxi, Ganzhou 341000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"e_1_2_7_1_1","unstructured":"\u00a0"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15514"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2016.10.004"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201904058"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.02.006"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.1c02790"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-022-01125-0"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c01852"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202215307"},{"key":"e_1_2_7_10_2","author":"Ding B.","year":"2023","journal-title":"Angew. 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