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Our preliminary bioinformatic data uncovered that elevated expression of SLC1A5, a critical Gln transporter, confers poor prognosis in breast cancer, underscoring its potential as a therapeutic target for metabolic regulation. Encouraged by this, this work proposes to enhance ferroptosis of breast cancer by inhibiting SLC1A5. As a proof\u2010of\u2010concept, we develop a nanoplatform for ferroptosis named MICLM, which is obtained by encapsulating chlorin e6 (Ce6, a photosensitizer) and IMD\u20100354 (an SLC1A5 inhibitor) into metal\u2010organic framework (NH\n                    <jats:sub>2<\/jats:sub>\n                    \u2010MIL\u2010101(Fe)), followed by surface coating for tumor\u2010targeting. Experimental data reveal that Ce6\u2010based photodynamic therapy synergizes with iron\u2010mediated Fenton reaction, potently driving lipid peroxides (LPOs) accumulation and triggering ferroptosis of 4T1 cells. Meanwhile, IMD\u20100354\u2010mediated Gln metabolic intervention is proven to inhibit glutathione (GSH) synthesis and activate lipophagy, thereby increasing free fatty acids (FFA) levels as an essential \u201cfuel\u201d for lipid peroxidation and overcoming a key limitation in ferroptosis efficacy. Additionally, Gln metabolism inhibition attenuates immunosuppressive M2 macrophage polarization, ultimately boosting antitumor immunity. Thus, MICLM effectively induces ferroptosis and remodels the tumor immune microenvironment via amino acid metabolic intervention, offering a promising strategy for ferroptosis\u2010based therapy.\n                  <\/jats:p>","DOI":"10.1002\/adhm.70969","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T12:36:13Z","timestamp":1771590973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Glutamine\u2010Metabolism\u2010Intervening Nanoplatform Activates Lipophagy to Potentiate Ferroptosis and Immune Activation in Breast Cancer"],"prefix":"10.1002","volume":"15","author":[{"given":"Jiayue","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Shandong Key Laboratory of Targeted Drug Delivery and Advanced Pharmaceutics Key Laboratory of Chemical Biology (Ministry of Education) NMPA Key Laboratory for Technology Research and Evaluation of Drug Products School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University Jinan Shandong P. 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