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HighlightsMnO 2 @Ce6 nanoprobes-loaded-iPS cells (iPS-MnO 2 @Ce6) were developed for enhanced photodynamic and immunotherapy against cancer.    Under the guidance of multi-mode real-time imaging, iPS-MnO 2 @Ce6 achieved an enhanced photodynamic therapeutic effect and stimulated a strong anti-tumor immune response in the tumor-bearing mouse.Abstract  How to trigger strong anti-tumor immune responses has become a focus for tumor therapy. Here, we report the human-induced pluripotent stem cells (iPSs) to deliver MnO 2 @Ce6 nanoprobes into tumors for simultaneous photodynamic therapy (PDT) and enhanced immunotherapy. Ce6 photosensitizer was attached on manganese dioxide (MnO 2 ) nanoparticles, and resultant MnO 2 @Ce6 nanoprobes were delivered into mitomycin-treated iPSs to form iPS-MnO 2 @Ce6 nanoprobes. The iPS-MnO 2 @Ce6 actively targeted in vivo tumors, the acidic microenvironment triggered interaction between MnO 2  and H 2 O 2 , released large quantities of oxygen, alleviated hypoxia in tumor. Upon PDT, singlet oxygen formed, broken iPSs released tumor-shared antigens, which evoked an intensive innate and adaptive immune response against the tumor, improving dendritic cells matured, effector T cells, and natural killer cells were activated. Meanwhile, regulatory T cells were reduced, and then the immune response induced by iPS-MnO 2 @Ce6 was markedly stronger than the immune reaction induced by MnO 2 @Ce6 ( P  < 0.05). The iPS-MnO 2 @Ce6 markedly inhibited tumor growth and metastasis and reduced mortality in mice models with tumor. Human iPSs loaded with MnO 2 -based nanoprobes are a promising strategy for simultaneous PDT and enhanced immunotherapy against tumor and own clinical translational prospect.Electronic supplementary material  The online version of this article (10.1007/s40820-020-00452-y) contains supplementary material, which is available to authorized users.

Human iPS Cells Loaded with MnO2-Based Nanoprobes for Photodynamic and Simultaneous Enhanced Immunotherapy Against Cancer