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Current strategies in nanomedicine for inducing ferroptosis primarily focus on promoting the accumulation of reactive oxygen species (ROS). However, the presence of intracellular antioxidants, such as nuclear factor erythroid 2\u2010related factor 2 (Nrf2), can limit the effectiveness of such therapy by activating detoxification systems and eliminating ROS. To overcome this challenge, we developed a synergistic ferroptosis\u2010inducing agent\u00a0by modifying manganese (Mn<jats:sup>2+<\/jats:sup>)\u20131,8\u2010dihydroxy\u20103\u2010hydroxymethyl\u2010anthraquinone (aloe\u2010emodin, AE) with polyvinyl pyrrolidone (PVP) to create nanoparticles (MAP NPs). In the tumor microenvironment, these NPs degraded and released AE and Mn(II), facilitating the generation of ROS and Mn(IV) through a Fenton\u2010like reaction between hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) and Mn(II). Mn(IV) subsequently interacts with glutathione (GSH) to induce a cyclic catalytic effect, and the depletion of GSH diminished the activation of glutathione\u2010dependent peroxidase 4 (GPX4). Furthermore, AE inhibits the activity of Nrf2 and depleted GSH, thereby synergistically enhancing antitumor efficacy. Here it is demonstrated that MAP NPs effectively generate a robust ROS storm within tumor cells, suggesting that high\u2010performance ferroptosis therapy is effective. Additionally, the inclusion of Mn(II) in the MAP NPs enables real\u2010time monitoring of therapeutic efficacy via magnetic resonance <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub>\u2010weighted contrast imaging.<\/jats:p>","DOI":"10.1002\/adhm.202400474","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T16:34:06Z","timestamp":1718382846000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Mn(II)\u2010Aloe\u2010Emodin Nanoscale Coordination Polymer Enhances Ferroptosis by Synergistically Enhancing Reactive Oxygen Species Generation via the Nrf2\u2013GPX4 Axis"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaoxin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Radiology Second Xiangya Hospital of Central South University  Changsha 410011 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