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The system (DOX@MIL\u2010LOX@AL) is fabricated by packaging alginate on the surface of Doxorubicin (DOX) and lactate oxidase (LOX) loaded MIL\u2010101(Fe)\u2010NH<jats:sub>2<\/jats:sub> nanoparticle, which can easily aggregate in the tumor microenvironment through the cross\u2010linking with intratumoral Ca<jats:sup>2+<\/jats:sup>. Benefiting from the tumor retention ability, the fast\u2010formed drug depository will continuously release DOX and Fe ions through the ATP\u2010triggered slow degradation, thus realizing persistent antitumor chemotherapy and immune regulation. Meanwhile, LOX in the non\u2010aggregated nanoparticles is able to convert the lactic acid to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, which will be subsequently decomposed into \u00b7OH by Fe ions to further enhance the DOX\u2010induced immunogenic death effect of tumor cells. Together, with the effective consumption of immunosuppressive lactic acid, long\u2010term chemotherapy, and oxidation therapy, DOX@MIL\u2010LOX@AL can execute high\u2010performance antitumor chemotherapy and immune activation with only one subcutaneous administration.<\/jats:p>","DOI":"10.1002\/smll.202307736","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T23:22:00Z","timestamp":1701127320000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Tumor Microenvironment\u2010Induced Drug Depository for Persistent Antitumor Chemotherapy and Immune Activation"],"prefix":"10.1002","volume":"20","author":[{"given":"Fan","family":"Gao","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control Collaborative Innovation Center of Atmospheric Environment and Equipment Technology School of Environmental Science and 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