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The repolarization of pro\u2010tumor M2 TAMs to anti\u2010tumor M1 TAMs is a very promising immunotherapeutic strategy for cancer therapy. In this manuscript, multifunctional 2D iron\u2010based nanosheets (FeNSs) are synthesized via a simple hydrothermal method for the first time, which not only possess photothermal and photodynamic properties, but also can repolarize TAMs from M2 to M1. After modifying with polyethylene glycol and loading with bioreductive prodrug banoxantrone (AQ4N), abbreviated as <jats:sub>AP<\/jats:sub>FeNSs, it can effectively repolarize TAMs from M2 to M1 and deliver AQ4N to tumor microenvironment (TME). Moreover, the repolarized M1 TAMs overexpress inducible nitric oxide synthase, which can convert nontoxic AQ4N to cytotoxic AQ4 under hypoxic TME, enabling immunomodulation\u2010activated chemotherapy. A series of in vitro and in vivo results corroborate that <jats:sub>AP<\/jats:sub>FeNSs effectively exert photothermal and photodynamic effects and repolarize M2 TAMs to M1 TAMs, releasing inflammatory factors and activating the chemotherapeutic effect, thereby realizing synergistic tumor therapy.<\/jats:p>","DOI":"10.1002\/adhm.202200776","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T06:29:37Z","timestamp":1659335377000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Functional 2D Iron\u2010Based Nanosheets for Synergistic Immunotherapy, Phototherapy, and Chemotherapy of Tumor"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7483-322X","authenticated-orcid":false,"given":"Xingbo","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory of Chemical Biology Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun Jilin 130022 P. 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