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Polarizing tumor\u2010associated macrophages (TAMs) and remodeling the immune\u2010deficient tumor microenvironment (TME) can enhance T lymphocyte recruitment and infiltration. However, the immune privilege and low immunogenic responses of these aggressive tumor clusters often limit lymphocyte recruitment. Here, an M1 macrophage membrane\u2010coated iron oxide nanoparticle (IO@MM) double as a tumor\u2010penetrated agent and na\u00efve M0 macrophage to M1 polarizer is developed for lung metastatic colorectal cancer (CRC) immunotherapy. At the tumor site, IO@MM combined with resiquimod (R848) increased the immune cell infiltration, turning the \u201cCold\u201d TME into an immune\u2010activating \u201cHot\u201d one. Together with self\u2010cascade immunotherapy, IO@MM with R848 promotes tumor release of damage\u2010associated molecular patterns (DAMPs). At the same time, IO@MM uses the membrane as an antigen reservoir and provides autologous DAMPs to retain dendritic cells. This IO@MM effectively inhibits tumors and improves survival rate as an immunomodulator in lung metastasis.<\/jats:p>","DOI":"10.1002\/smll.202406790","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T04:14:57Z","timestamp":1732248897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Reprogrammed Lung Metastasis Immunodeficiency via Targeted Penetrated Delivery of M1 Macrophage\u2010Wrapped NanoCubes\u2010Mediated T Cell Infiltration"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4191-5274","authenticated-orcid":false,"given":"Kang\u2010Li","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Environmental Sciences National Tsing Hua University  Hsinchu 300044 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