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Furthermore, RBCs possess the ability to stably bind therapeutic gas molecules such as carbon monoxide (CO) and nitric oxide (NO). As natural gas carriers, RBCs have the potential to mitigate the non\u2010specific gas release and biosafety issues associated with conventional gas donors, which currently hinder the clinical application of gas therapy. In this study, RBCs are innovatively engineered for amplified tumor dual\u2010gas transfusion therapy. The RBCs delivering CO and NO are developed using advanced nano\u2010 and gas\u2010engineering techniques. These engineered RBCs are activated by tumor cell\u2010specific\u00a0hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) to release gases, and it induces a cascade amplification of reactive oxygen species (ROS) and reactive nitrogen species (RNS) (ONOO<jats:sup>\u2212<\/jats:sup>) production through the catalytic action of the ferrous hemoglobin (HbFe<jats:sup>2+<\/jats:sup>). This process disrupts glycometabolism and reshapes the tumor immunosuppressive microenvironment, thereby enhancing therapeutic efficacy. By integrating tumor cell membrane engineering, this approach enables targeted, personalized therapy and effectively suppresses metastatic tumors synergistically with <jats:italic>\u03b1<\/jats:italic>PD\u2010L1. Comprehensive evaluation demonstrates that engineered RBC\u2010based amplified tumor dual\u2010gas transfusion therapy exhibits excellent biosafety, and holds significant potential as a highly translatable and promising cancer treatment modality.<\/jats:p>","DOI":"10.1002\/adma.202503206","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T11:35:26Z","timestamp":1749036926000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Engineering Red Blood Cells for Amplified Tumor Dual\u2010Gas Transfusion Therapy"],"prefix":"10.1002","volume":"37","author":[{"given":"Tao","family":"Li","sequence":"first","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening School of Pharmaceutical Sciences Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Ouyang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; 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