{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:08:16Z","timestamp":1789060096110,"version":"build-2803163510"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Breast cancer is the most diagnosed malignancy and major cause of cancer death among women population in the worldwide. Ferroptosis is a recently discovered iron-dependent regulated cell death involved in tumor progression and therapeutic response. Moreover, increasing studies have implied that ferroptosis is a promising approach to eliminating cancer cells like developing iron nanoparticles as a therapeutic agent. However, resistance to ferroptosis is a vital distinctive hallmark of cancer. Therefore, further investigation of the mechanism of ferroptosis resistance to enhance its tumor sensitivity is essential for ferroptosis-target breast cancer therapy. Our results revealed that the activation of C5a\/C5aR pathway can drive resistance to ferroptosis and reshaping breast cancer immune microenvironment. Accordingly, loading PEG-Fe<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub> with C5aRA significantly improved the anti-tumor effect of PEG- Fe<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub> by inhibiting ferroptosis resistance and increasing macrophage polarization toward M1 phenotype. Our findings presented a novel cancer therapy strategy that combined cancer cell metal metabolism regulation and immunotherapy. The study also provided support for further evaluation of PEG- Fe<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub>@C5aRA as a novel therapeutic strategy for breast cancer in clinical trials.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1466180","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T04:25:35Z","timestamp":1729139135000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["A novel hollow iron nanoparticle system loading PEG-Fe3O4 with C5a receptor antagonist for breast cancer 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