biostudies-literatureChen YNational Natural Science Foundation of China13817-13824https://www.ebi.ac.uk/biostudies/studies/S-EPMC8549783biostudies-literatureUnknown12(41)Spatiotemporally activatable immune cells are promising for tumor immunotherapy owing to their potential high specificity and low side effects. Herein, we developed an X-ray-induced phenotypic transformation (X-PT) strategy through macrophage engineering for safe and efficient tumor immunotherapy. Without complex genetic engineering, the cell membranes of M0-type macrophages were chemically engineered with AS1411 aptamer-based polyvalent spherical aptamer (PSA) <i>via</i> the combination of metabolic glycan labelling and bioorthogonal click reaction. Owing to the superior specificity, affinity and polyvalent binding effects of the high-density AS1411 aptamers, the engineered macrophages could easily recognize and adhere to tumor cells. With further X-ray irradiation, reactive oxygen specieChemical sciencePolyvalent spherical aptamer engineered macrophages: X-ray-actuated phenotypic transformation for tumor immunotherapy.PMC85497832187408621927811Pan WGao PShi MTang BChen YLiu SLi NfalsePolyvalent spherical aptamer engineered macrophages: X-ray-actuated phenotypic transformation for tumor immunotherapy.Spatiotemporally activatable immune cells are promising for tumor immunotherapy owing to their potential high specificity and low side effects. Herein, we developed an X-ray-induced phenotypic transformation (X-PT) strategy through macrophage engineering for safe and efficient tumor immunotherapy. Without complex genetic engineering, the cell membranes of M0-type macrophages were chemically engineered with AS1411 aptamer-based polyvalent spherical aptamer (PSA) <i>via</i> the combination of metabolic glycan labelling and bioorthogonal click reaction. Owing to the superior specificity, affinity and polyvalent binding effects of the high-density AS1411 aptamers, the engineered macrophages could easily recognize and adhere to tumor cells. With further X-ray irradiation, reactive oxygen specie2021-01-01T00:00:00Z2021 Oct2026-05-08T17:05:41.311Z2022-02-11T12:42:07.457ZS-EPMC85497833476016710.1039/d1sc03997k