Nano-Micro Letters

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

Yanlei Liu1, #, Jingxing Yang3, #, Bin Liu1, Wen Cao1, Jingpu Zhang4, Yuming Yang1, Lijun Ma5, Jesus Martinez de la Fuente1, Jie Song1, Jian Ni1, Chunfu Zhang3, *, Daxiang Cui1, 2, *

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Nano-Micro Lett. (2020) 12: 127

First Online: 16 June 2020 (Article)

DOI:10.1007/s40820-020-00452-y

*Corresponding author. E-mail: dxcui@sjtu.edu.cn (Daxiang Cui), cfzhang@sjtu.edu.cn (Chunfu Zhang)

 

Abstract

 


Toc

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, 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 MnO2 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 is a promising strategy for simultaneous PDT and enhanced immunotherapy against tumor, and owns clinical translational prospect.


 

Keywords

Human iPS; MnO2@Ce6 nanoprobes; Photodynamic therapy; Immunotherapy; Cancer

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