{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:58:24Z","timestamp":1792011504078,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:00:00Z","timestamp":1700697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004733","name":"Universidade de Macau","doi-asserted-by":"publisher","award":["MYRG2022\u201000203\u2010ICMS"],"award-info":[{"award-number":["MYRG2022\u201000203\u2010ICMS"]}],"id":[{"id":"10.13039\/501100004733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006469","name":"Fundo para o Desenvolvimento das Ci\u00eancias e da Tecnologia","doi-asserted-by":"publisher","award":["0096\/2020\/AMJ"],"award-info":[{"award-number":["0096\/2020\/AMJ"]}],"id":[{"id":"10.13039\/501100006469","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ferroptosis\u2010related cancer therapy is limited by insufficient Fe\n                    <jats:sup>2+<\/jats:sup>\n                    \/Fe\n                    <jats:sup>3+<\/jats:sup>\n                    redox pair and hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) for producing lethal hydroxyl radicals (\u00b7OH). Although exogenous iron or ROS\u2010producing drugs can enhance ferroptosis, exploiting endogenous iron (labile iron pool, LIP) stored in ferritin and promoting ROS generation may be safer. Herein, a metal\/drug\u2010free nanomedicine is developed for responsive LIP release and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    generation on the mitochondria membranes, amplifying hydroxyl radical production to enhance ferroptosis\u2010mediated antitumor effects. A glutathione(GSH)\/pH dual activatable fluorinated and cross\u2010linked polyethyleneimine (PEI) with dialdehyde polyethylene glycol layer nanocomplex loaded with MTS\u2010KR\u2010SOD (Mitochondria\u2010targeting\u2010sequence\u2010KillerRed\u2010Superoxide Dismutase) and CRISPR\/Cas9\u2010CA IX (Carbonic anhydrase IX (CA IX)) plasmids (FP@MC) are developed for enhanced ferroptosis through endogenous iron de\u2010hijacking and in situ ROS amplification. Two plasmids are constructed to knockdown CA IX and translate KillerRed\u2010SOD recombinant protein specifically on mitochondria membranes, respectively. The CA IX knockdown acidifies the intracellular environment, leading the release of LIP from ferritin as a \u201cflare\u201d to initiate endogenous chemodynamic therapy. Meanwhile, MTS\u2010KR\u2010SOD generates H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    when irradiated by a 590\u00a0nm laser to assist chemodynamic therapy, leading to ROS amplification for mitochondria damage and lipid peroxide accumulation. The combined therapeutic effects aggravate cancer ferroptosis and suppress tumor growth, providing a new paradigm for amplifying ROS and iron ions to promote ferroptosis\u2010related cancer therapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.202304098","type":"journal-article","created":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T02:18:09Z","timestamp":1694312289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["GSH\/pH Dual Activatable Cross\u2010linked and Fluorinated PEI for Cancer Gene Therapy Through Endogenous Iron De\u2010Hijacking and in Situ ROS Amplification"],"prefix":"10.1002","volume":"36","author":[{"given":"Suleixin","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macau SAR 999078 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