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Thus, it is necessary to develop a synergistic strategy with high tumor targeting specificity to enhance the mortality of GOX. In this study, a genetically engineered CD44 targeting peptide (CP) and IL\u201021 fusion protein\u2010displaying nanovesicles platform (mCP@IL21\u2010Fc\u2010GOX) are designed to efficiently encapsulate GOX and ferrocene (Fc). After reaching the tumor site, IL\u201021 can be precisely released and targeted to NK cells through the cleavage of MMP\u20102, thus achieving precise anti\u2010tumor immunotherapy of IL\u201021. Second, the exposed CP enable mCP\u2010Fc\u2010GOX to be further targeted to tumor cells, completing the synergistic anti\u2010cancer effects of starvation and chemodynamic therapy (CDT) triggered by GOX and Fc. In situ breast cancer models, the results show that mCP@IL21\u2010Fc\u2010GOX not only enhances NK and T cells aggregation in tumor tissue but also achieves precise nutrition deprivation and abundant reactive oxygen species production, thus significantly inhibits tumor growth based on the synergistic function of the immunotherapy, starvation and CDT. Therefore, this work provides a smart nanovesicle platform for achieving precise and safe synergistic anti\u2010tumor therapy.<\/jats:p>","DOI":"10.1002\/adhm.202403477","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:58:58Z","timestamp":1736211538000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Engineered IL\u201021\u2010Expressing Nanovesicles for Co\u2010Delivery of GOX and Ferrocene to Induce Synergistic Anti\u2010Tumor Effects"],"prefix":"10.1002","volume":"14","author":[{"given":"Chao","family":"Li","sequence":"first","affiliation":[{"name":"School of Life Sciences Anhui Medical University  Hefei Anhui 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyang","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Life Sciences Anhui Medical University  Hefei Anhui 230032 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