{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:57:34Z","timestamp":1790693854243,"version":"4.1.0"},"reference-count":302,"publisher":"American Chemical Society (ACS)","issue":"38","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20158"],"award-info":[{"award-number":["U22A20158"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Funds for Central Universities"},{"name":"State Key Laboratory of Advanced Polymer Materials","award":["sklapm2025-2-03"],"award-info":[{"award-number":["sklapm2025-2-03"]}]},{"name":"Sichuan Science and Technology Program","award":["2026NSFSC1371"],"award-info":[{"award-number":["2026NSFSC1371"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ferroptosis, a unique form of regulated, iron-dependent cell death, has emerged as a therapeutic mechanism for a range of diseases, including cancer, neurodegeneration, metabolic disorders, and organ injuries. However, the clinical translation of small-molecule ferroptosis modulators remains limited due to poor specificity, pharmacokinetic instability, and insufficient targeting capability. In contrast, nanomaterials offer a highly tunable and multifunctional platform for ferroptosis modulation, enabling precise delivery, spatiotemporal control, and synergistic therapeutic effects. This review presents a comprehensive synthesis of nanomaterial-based strategies for ferroptosis modulation, emphasizing both induction in cancer therapy and inhibition in non-cancer diseases. We first summarize the molecular mechanisms governing ferroptosis and rational design strategies for nanomaterials targeting ferroptosis-related pathways. We then discuss recent advances in nanomaterial-mediated ferroptosis induction for cancer therapy, and their application of ferroptosis inhibition for treating non-cancer diseases, including inflammatory organ injuries, neurological disorders, and metabolic degeneration. By systematically linking nanomaterial molecular and structural design with ferroptosis regulation mechanisms, this review highlights the dual regulatory role of nanomaterials in both inducing and inhibiting ferroptosis and provides design guidelines for the rational development of ferroptosis-targeting nanomedicines for precision therapy.<\/jats:p>","DOI":"10.1021\/acsnano.6c10760","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:02:06Z","timestamp":1789556526000},"page":"25956-25992","source":"Crossref","is-referenced-by-count":0,"title":["Rational Nanomaterial\nDesign for Ferroptosis Modulation:\nBidirectional Therapeutic Strategies in Cancer and Beyond"],"prefix":"10.1021","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3631-1299","authenticated-orcid":true,"given":"Zhongqiang","family":"Zhu","sequence":"first","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1003-850X","authenticated-orcid":true,"given":"Ling","family":"Jiang","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China , , ,","place":["Chengdu, China, 610072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Sun","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1835-6825","authenticated-orcid":true,"given":"Xingyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Southwest Jiaotong University , , ,","place":["Chengdu, China, 610031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0893-9798","authenticated-orcid":true,"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1522-7326","authenticated-orcid":true,"given":"Jianshu","family":"Li","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610065"]},{"name":"Sichuan University , , ,","place":["Chengdu, China, 610041"]},{"name":"Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"issue":"2","key":"2026092909141075600_cit1","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A Regulated\nCell Death Nexus Linking Metabolism, Redox Biology, and Disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"issue":"3","key":"2026092909141075600_cit2","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.molcel.2025.11.013","article-title":"The Landscape\nof Regulated Cell Death:\nIt\u2019s All Downhill from Here","volume":"86","author":"Aufschnaiter","year":"2026","journal-title":"Mol. 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Mol.\nImmunol."},{"issue":"7534","key":"2026092909141075600_cit4","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/nature14191","article-title":"Necroptosis and Its Role in Inflammation","volume":"517","author":"Pasparakis","year":"2015","journal-title":"Nature"},{"issue":"8","key":"2026092909141075600_cit5","doi-asserted-by":"publisher","first-page":"2322","DOI":"10.1016\/j.cell.2026.03.024","article-title":"Cell Death in Cancer","volume":"189","author":"Conrad","year":"2026","journal-title":"Cell"},{"issue":"5","key":"2026092909141075600_cit6","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An Iron-Dependent Form of Nonapoptotic\nCell Death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"issue":"35","key":"2026092909141075600_cit7","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202300379","article-title":"Ferroptosis Detection:\nFrom Approaches to Applications","volume":"62","author":"Zeng","year":"2023","journal-title":"Angew. 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Mol. Sci."},{"issue":"4","key":"2026092909141075600_cit12","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: Mechanisms, Biology\nand Role in Disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"1","key":"2026092909141075600_cit13","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-025-02567-5","article-title":"Ferroptosis in Cancer\ntoward Molecular Insights and Clinical Translation in Pancreatic Cancer","volume":"25","author":"Chen","year":"2026","journal-title":"Mol. 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Oncol."},{"key":"2026092909141075600_cit18","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.canlet.2018.06.018","article-title":"CISD2 Inhibition\nOvercomes Resistance to Sulfasalazine-Induced Ferroptotic Cell Death\nin Head and Neck Cancer","volume":"432","author":"Kim","year":"2018","journal-title":"Cancer Lett."},{"issue":"1","key":"2026092909141075600_cit19","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.canlet.2016.07.035","article-title":"Induction\nof Ferroptotic Cell Death for Overcoming Cisplatin Resistance of Head\nand Neck Cancer","volume":"381","author":"Roh","year":"2016","journal-title":"Cancer Lett."},{"issue":"8","key":"2026092909141075600_cit20","doi-asserted-by":"publisher","first-page":"3401","DOI":"10.1021\/acs.nanolett.3c00365","article-title":"Depriving Tumor Cells of Ways to\nMetastasize: Ferroptosis\nNanotherapy Blocks Both Hematogenous Metastasis and Lymphatic Metastasis","volume":"23","author":"Guo","year":"2023","journal-title":"Nano Lett."},{"key":"2026092909141075600_cit21","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102703","article-title":"The\nFerroptosis Inducing Compounds RSL3 and ML162 Are not Direct Inhibitors\nof GPX4 but of TXNRD1","volume":"62","author":"Cheff","year":"2023","journal-title":"Redox Biol."},{"issue":"11","key":"2026092909141075600_cit22","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04306-2","article-title":"Fin56-Induced Ferroptosis\nis Supported by Autophagy-Mediated GPX4 Degradation and Functions\nSynergistically with mTOR Inhibition to Kill Bladder Cancer Cells","volume":"12","author":"Sun","year":"2021","journal-title":"Cell Death Dis."},{"issue":"14","key":"2026092909141075600_cit23","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1016\/j.cell.2022.06.003","article-title":"Ferroptosis\nTurns 10: Emerging Mechanisms, Physiological Functions, and Therapeutic\nApplications","volume":"185","author":"Stockwell","year":"2022","journal-title":"Cell"},{"issue":"21","key":"2026092909141075600_cit24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2317616121","article-title":"Lipid-Derived Electrophiles Inhibit\nthe Function of Membrane Channels during Ferroptosis","volume":"121","author":"Van Kessel","year":"2024","journal-title":"Proc. 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Metab."},{"issue":"2","key":"2026092909141075600_cit50","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/s41556-020-0461-8","article-title":"Energy-Stress-Mediated AMPK Activation Inhibits\nFerroptosis","volume":"22","author":"Lee","year":"2020","journal-title":"Nat. Cell Biol."},{"issue":"4","key":"2026092909141075600_cit51","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.bbrc.2018.12.039","article-title":"Lipid Storage\nand Lipophagy Regulates Ferroptosis","volume":"508","author":"Bai","year":"2019","journal-title":"Biochem.\nBiophys. Res. Commun."},{"issue":"1","key":"2026092909141075600_cit52","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nchembio.2239","article-title":"ACSL4\nDictates Ferroptosis\nSensitivity by Shaping Cellular Lipid Composition","volume":"13","author":"Doll","year":"2017","journal-title":"Nat. Chem. 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