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Consequently, the disruption of ferroptosis defense mechanisms could be lethal to these cancer cells, while sparing normal cells. Despite this potential, the development of effective and controlled in vivo therapies targeting ferroptosis remains underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, liposomes modified with Glu-urea-Lys (GUL) encapsulating Mn\n                      <jats:sub>0.6<\/jats:sub>\n                      Zn\n                      <jats:sub>0.4<\/jats:sub>\n                      Fe\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>4<\/jats:sub>\n                      (MZ) were employed as siRNA delivery vectors targeting Ying Yang 1 (YY1) for PCa treatment both in vitro and in vivo. The synergistic antitumor effects of the GUL@LsiYY1@MZ nanosystem were assessed using CCK8 assays, Western blot analysis, flow cytometry, and laser scanning confocal microscopy imaging in vitro. Additionally, the mechanisms underlying the ferroptosis effects were further explored through transcriptome and lipidomics sequencing. Intravenous administration was employed to treat subcutaneous tumors in a mouse model, and the tumor inhibitory effects, safety, and visibility on T\n                      <jats:sub>2<\/jats:sub>\n                      -weighted MRI were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The engineered GUL@LsiYY1@MZ nanosystem exploits the specific binding affinity of GUL for the prostate membrane-specific antigen (PSMA), facilitating targeted delivery and accumulation. Upon exposure to alternating magnetic fields (AMF), this system enables the precision-controlled release of siRNA into the cell, leading to the knockdown of YY1 expression. This downregulation subsequently affects the expression of the SLC7A11, thereby disrupting glutathione metabolism. Additionally, the introduction of excess Fe\n                      <jats:sup>2+<\/jats:sup>\n                      induces iron overload, further promoting ferroptosis. Significantly, this therapeutic intervention restructured the metabolism of PCa cells, leading to a substantial intracellular accumulation of unsaturated fatty acids. This accumulation provided an abundant substrate for the generation of phospholipid peroxides, ultimately compromising plasma membrane integrity and inducing ferroptosis in PCa cells. Furthermore, the nanosystem also functions as a contrast agent, enhancing the T\n                      <jats:sub>2<\/jats:sub>\n                      -weighted MRI imaging of solid tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The GUL@LsiYY1@MZ nanosystem utilizes AMF-triggered release to downregulate SLC7A11, inducing ferroptosis and contributing to enhanced anti-tumor efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13046-025-03530-4","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T12:39:19Z","timestamp":1759235959000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["PSMA-targeted theranostic nanoplatform achieves spatiotemporally precise therapy and triggers ferroptosis in prostate cancer treatment"],"prefix":"10.1186","volume":"44","author":[{"given":"Linxue","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongwen","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiji","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"issue":"1","key":"3530_CR1","first-page":"12","volume":"74","author":"R Siegel","year":"2024","unstructured":"Siegel R, Giaquinto A, Jemal A. 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ACS Nano. 2023;17(4):4009\u201322.","journal-title":"ACS Nano"}],"container-title":["Journal of Experimental &amp; Clinical Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-025-03530-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13046-025-03530-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-025-03530-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T11:26:39Z","timestamp":1781609199000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13046-025-03530-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,30]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3530"],"URL":"https:\/\/doi.org\/10.1186\/s13046-025-03530-4","relation":{},"ISSN":["1756-9966"],"issn-type":[{"value":"1756-9966","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,30]]},"assertion":[{"value":"21 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was approved by the Clinical Ethics Committee of Sichuan Provincial People\u2019s Hospital and the Animal Experimental Ethical Inspection of the University of Electronic Science and Technology of China. The animals were housed in a controlled environment with a temperature of 22\u2009\u00b1\u20092\u00a0\u00b0C, relative humidity of 50\u2009\u00b1\u200910%, and a 12-hour light\/dark cycle, with standard laboratory chow and water provided ad libitum. They were acclimatized to the housing conditions for at least 7 days before the initiation of the experiments. Since the magnetic hyperthermia treatment was non-invasive and did not induce pain or significant distress, no analgesia was administered during the procedure. Euthanasia was performed humanely at the end of the study using an overdose of anesthetic agents, and all efforts were made to minimize animal suffering. The study adhered to ethical standards for animal research.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have read and approved the final manuscript for publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"272"}}