Polyvalent spherical aptamer engineered macrophages: X-ray-actuated phenotypic transformation for tumor immunotherapy |
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Authors: | Yuanyuan Chen Peng Gao Wei Pan Mingwan Shi Shujie Liu Na Li Bo Tang |
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Institution: | College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014 P. R. China, |
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Abstract: | 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) via 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 species (ROS) generated by the Au-based PSA could efficiently transform the accumulated macrophages in situ from biocompatible M0 into antitumoral M1 phenotype via activating the nuclear factor κB signaling pathway, thereby achieving tumor-specific killing. In vitro and in vivo experiments confirmed the high tumor recognition and X-ray-induced polarization effect of the engineered macrophages. Compared to natural macrophages, our engineered macrophages significantly inhibited tumor growth in mice even if the radiation dose was reduced by three-fold. We believe this X-PT strategy will open a new avenue for clinical immune cell-based therapy.An X-ray-induced phenotypic transformation strategy (X-PT) through macrophage engineering was developed for safe and effective immunotherapy. |
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