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This study investigates the immunomodulatory effects of polyethylene glycol\u2010functionalized BP (BP\u2010PEG) nanosheets in breast cancer models. Using immunocompetent mouse models\u2010including 4T1 orthotopic BALB\/c mice and MMTV\u2010PyMT transgenic mice, it is found that BP\u2010PEG significantly inhibits tumor growth and metastasis without directly inducing cytotoxicity in tumor cells. Mass cytometry analysis reveals that BP\u2010PEG reshapes the tumor immune microenvironment by recruiting neutrophils. Neutrophil depletion experiments further demonstrate that the antitumor effects of BP\u2010PEG are dependent on neutrophils. Moreover, bulk and single\u2010cell RNA sequencing indicate that BP\u2010PEG is mainly taken up by macrophages, leading to the release of inflammatory factors such as IL1A and CXCL2, which enhance neutrophil recruitment and activation, thereby amplifying the antitumor immune response. Finally, co\u2010culture assays confirm that BP\u2010PEG indeed enhances the antitumor activity of neutrophils and natural killer (NK) cells. These findings position BP\u2010PEG as an immunomodulatory agent capable of reprogramming the tumor microenvironment to promote innate immunity against breast cancer. By stimulating neutrophil\u2010mediated antitumor activity, BP\u2010PEG offers a unique therapeutic approach that can potentially enhance the efficacy of existing cancer immunotherapies.<\/jats:p>","DOI":"10.1002\/advs.202414779","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T05:01:59Z","timestamp":1737522119000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Therapeutic Black Phosphorus Nanosheets Elicit Neutrophil Response for Enhanced Tumor Suppression"],"prefix":"10.1002","volume":"12","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of General Surgery The First Affiliated Hospital of University of Science and Technology of China Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui 230036 P. R. 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