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M1\u2010like macrophage\u2010derived exosomes (M1\u2010Exos) have emerged as a promising tumor therapeutic candidate for their tumor\u2010targeting and macrophage\u2010polarization capabilities. However, the limited drug\u2010loading efficiency and stability of M1\u2010Exos have hindered their effectiveness in antitumor applications. Here, a hybrid nanovesicle is developed by integrating M1\u2010Exos with AS1411 aptamer\u2010conjugated liposomes (AApt\u2010Lips), termed M1E\/AALs. The obtained M1E\/AALs are loaded with\u00a0perfluorotributylamine (PFTBA)\u00a0and IR780, as P\u2010I, to construct P\u2010I@M1E\/AALs for reprogramming TME by alleviating tumor hypoxia and engineering TAMs. P\u2010I@M1E\/AAL\u2010mediated tumor therapy enhances the in situ generation of reactive oxygen species, repolarizes TAMs toward an antitumor phenotype, and promotes the infiltration of T lymphocytes. The synergistic antitumor therapy based on P\u2010I@M1E\/AALs significantly suppresses tumor growth and prolongs the survival of 4T1\u2010tumor\u2010bearing mice. By integrating multiple treatment modalities, P\u2010I@M1E\/AAL nanoplatform demonstrates a promising therapeutic approach for overcoming hypoxic and immunosuppressive TME by targeted TAM reprogramming and enhanced tumor photodynamic immunotherapy. This study highlights an innovative TAM\u2010engineering hybrid nanovesicle platform for the treatment of tumors characterized by hypoxic and immunosuppressive TME.<\/jats:p>","DOI":"10.1002\/adma.202401495","type":"journal-article","created":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T01:28:55Z","timestamp":1717896535000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Biointerface\u2010Engineered Hybrid Nanovesicles for Targeted Reprogramming of Tumor Microenvironment"],"prefix":"10.1002","volume":"36","author":[{"given":"Xueyan","family":"Zhen","sequence":"first","affiliation":[{"name":"School of Pharmacy, Health Science Center Xi'an Jiaotong University  Xi'an 710061 China"},{"name":"Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital Harvard Medical School  Boston MA 02115 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