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

Nano-Micro Letters (Jun 2020)

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

Affiliations

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
Jingxing Yang: Department of Nuclear Medicine, Rui Jin Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University
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
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
Jingpu Zhang: Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University
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
Lijun Ma: Tongren Hospital, Shanghai Jiao Tong University School of Medicine
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
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
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
Chunfu Zhang: Department of Nuclear Medicine, Rui Jin Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University
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

DOI: https://doi.org/10.1007/s40820-020-00452-y
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 17

Abstract

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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.

Published in Nano-Micro Letters

ISSN: 2311-6706 (Print); 2150-5551 (Online)
Publisher: SpringerOpen
Country of publisher: Germany
LCC subjects: Technology
Website: http://www.springer.com/40820

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