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Vol. 12 (2020)

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

https://doi.org/10.1007/s40820-020-00452-y
Yanlei Liu
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
Jingxing Yang
Department of Nuclear Medicine, Rui Jin Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China
Bin Liu
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
Wen Cao
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
Jingpu Zhang
Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, People’s Republic of China
Yuming Yang
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
Lijun Ma
Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai 200336, People’s Republic of China
Jesus Martinez de la Fuente
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
Jie Song
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
Jian Ni
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
Chunfu Zhang
Department of Nuclear Medicine, Rui Jin Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China
Daxiang Cui
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

Corresponding Author: Daxiang Cui

dxcui@sjtu.edu.cn

Nano-Micro Letters, Vol. 12 (2020), Article Number: 127

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.


Highlights:


1 MnO2@Ce6 nanoprobes-loaded-iPS cells (iPS-MnO2@Ce6) were developed for enhanced photodynamic and immunotherapy against cancer.
2 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.

Keywords

Human iPS MnO2@Ce6 nanoprobes Photodynamic therapy Immunotherapy Cancer
Liu, Yanlei, Jingxing Yang, Bin Liu, Wen Cao, Jingpu Zhang, Yuming Yang, Lijun Ma, Jesus Martinez de la Fuente, Jie Song, Jian Ni, Chunfu Zhang, and Daxiang Cui. 2020. “Human IPS Cells Loaded With MnO2-Based Nanoprobes for Photodynamic and Simultaneous Enhanced Immunotherapy Against Cancer”. Nano-Micro Letters 12 (June):127. https://doi.org/10.1007/s40820-020-00452-y.
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