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 MnO2@Ce6 nanoprobes into tumors for simultaneous photodynamic therapy (PDT) and enhanced immunotherapy. Ce6 photosensitizer was attached on manganese dioxide (MnO2) nanoparticles, and resultant MnO2@Ce6 nanoprobes were delivered into mitomycin-treated iPSs to form iPS-MnO2@Ce6 nanoprobes. The iPS-MnO2@Ce6 actively targeted in vivo tumors, the acidic microenvironment triggered interaction between MnO(2)and H2O2, 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-MnO2@Ce6 was markedly stronger than the immune reaction induced by MnO2@Ce6 (P < 0.05). The iPS-MnO2@Ce6 markedly inhibited tumor growth and metastasis and reduced mortality in mice models with tumor. Human iPSs loaded with MnO2-based nanoprobes are a promising strategy for simultaneous PDT and enhanced immunotherapy against tumor and own clinical translational prospect.
基金:
National Nature Scientific foundation [81803094, 81802979, 81921002]; National Foundational Basic Research Project of China [2017YFA0205301, 2015CB931802]; Shanghai Municipal Commission of Economy and Information Technology Fund [XC-ZXSJ-02-2016-05]; medical engineering cross project of Shanghai Jiao Tong university [YG2017ZD05, YG2016ZD10, YG2017Z D05]; Project of Thousand Youth Talents from China; National Key Research and Development Program of China [2017YFC1200904, 2017YFE0124400]
Liu Yanlei,Yang Jingxing,Liu Bin,et al.Human iPS Cells Loaded with MnO2-Based Nanoprobes for Photodynamic and Simultaneous Enhanced Immunotherapy Against Cancer[J].NANO-MICRO LETTERS.2020,12(1):doi:10.1007/s40820-020-00452-y.
APA:
Liu, Yanlei,Yang, Jingxing,Liu, Bin,Cao, Wen,Zhang, Jingpu...&Cui, Daxiang.(2020).Human iPS Cells Loaded with MnO2-Based Nanoprobes for Photodynamic and Simultaneous Enhanced Immunotherapy Against Cancer.NANO-MICRO LETTERS,12,(1)
MLA:
Liu, Yanlei,et al."Human iPS Cells Loaded with MnO2-Based Nanoprobes for Photodynamic and Simultaneous Enhanced Immunotherapy Against Cancer".NANO-MICRO LETTERS 12..1(2020)