Human iPS Cells Loaded with MnO 2 -Based Nanoprobes for Photodynamic and Simultaneous Enhanced Immunotherapy Against Can
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ARTICLE
Cite as Nano-Micro Lett. (2020) 12:127 Received: 17 March 2020 Accepted: 28 April 2020 © The Author(s) 2020
https://doi.org/10.1007/s40820-020-00452-y
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 * Yanlei Liu and Jingxing Yang have contributed equally to this work. * Chunfu Zhang, [email protected]; Daxiang Cui, [email protected] 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
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National Engineering Center for Nanotechnology, Shanghai 200240, People’s Republic of China Department of Nuclear Medicine, Rui Jin Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, People’s Republic of China Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai 200336, People’s Republic of China
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
633 nm Laser
pluripotent stem cells (iPSs) to deliver M nO2@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
Photodynamic therapy + immunotherapy
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 M nO2@Ce6 (P
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