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The TME of solid tumors is characterized by weak acidity, hypoxia, and elevated reactive oxygen species (ROS) levels, which collectively impair the function and persistence of infiltrating CAR\u2010T cells. In this study, acid\u2010sensitive responsive CaMnCO\n                    <jats:sub>3<\/jats:sub>\n                    nanoparticles (CMC NPs), are developed that simultaneously mitigate TME acidosis and hypoxia. IL\u201021 is encapsulated within CMC NPs (denoted as CMC\u201021), which are then surface\u2010conjugated to CAR\u2010T cells as functional \u2018vitality backpacks\u2019 to enhance cellular activity. The CMC\u201021 backpack enables sustained release of IL\u201021, persistently enhancing CAR\u2010T cell antitumor immunity across both low\u2010 and high\u2010dose infusion regimens. Furthermore, CMC NPs exert dual modulatory effects on the TME by: 1) consuming protons to neutralize acidic conditions, and 2) catalytically converting endogenous H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    to O\n                    <jats:sub>2<\/jats:sub>\n                    to relieve hypoxia. This multimodal remodeling of the immunosuppressive TME significantly enhances the infiltration and activity of adoptively transferred CAR\u2010T cells while simultaneously boosting endogenous T cell and NK cell recruitment in vivo. These findings establish a novel CAR\u2010T cell enhancement strategy through sustained IL\u201021 release from CMC\u201021 backpacks, offering new possibilities for solid tumor immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/smll.202501645","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T06:15:22Z","timestamp":1746771322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["IL\u201021 Loading CaMnCO\n                    <sub>3<\/sub>\n                    Vitality Backpacks Boost CAR\u2010T Cell Synergistic Immunotherapy"],"prefix":"10.1002","volume":"21","author":[{"given":"Baihui","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong 250021 P. R. 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