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

Yanlei Liu; Jingxing Yang; Bin Liu; Wen Cao; Jingpu Zhang; Yuming Yang; Lijun Ma; Jesus Martinez de la Fuente; Jie Song; Jian Ni; Chunfu Zhang; Daxiang Cui

doi:10.1007/s40820-020-00452-y

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

Nanomicro Lett. 2020 Jun 16;12(1):127. doi: 10.1007/s40820-020-00452-y.

Authors

Yanlei Liu^#¹, Jingxing Yang^#², Bin Liu¹, Wen Cao¹, Jingpu Zhang³, Yuming Yang¹, Lijun Ma⁴, Jesus Martinez de la Fuente¹, Jie Song¹, Jian Ni¹, Chunfu Zhang⁵, Daxiang Cui^{6

7}

Affiliations

¹ Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication of Ministration of Education, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People's Republic of China.
² Department of Nuclear Medicine, Rui Jin Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
³ Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People's Republic of China.
⁴ Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai, 200336, People's Republic of China.
⁵ Department of Nuclear Medicine, Rui Jin Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China. cfzhang@sjtu.edu.cn.
⁶ Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication of Ministration of Education, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People's Republic of China. dxcui@sjtu.edu.cn.
⁷ National Engineering Center for Nanotechnology, Shanghai, 200240, People's Republic of China. dxcui@sjtu.edu.cn.

^# Contributed equally.

Abstract

Highlights:

MnO₂@Ce6 nanoprobes-loaded-iPS cells (iPS-MnO₂@Ce6) were developed for enhanced photodynamic and immunotherapy against cancer.
Under the guidance of multi-mode real-time imaging, iPS-MnO₂@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 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 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 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.

Keywords: Cancer; Human iPS; Immunotherapy; MnO2@Ce6 nanoprobes; Photodynamic therapy.