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

作     者：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 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

作者机构：Institute of Nano Biomedicine and EngineeringKey Laboratory for Thin Film and Microfabrication of Ministration of EducationShanghai Engineering Research Centre for Intelligent Diagnosis and Treatment InstrumentDepartment of Instrument Science and EngineeringSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong University800 Dongchuan RoadShanghai 200240People’s Republic of China National Engineering Center for NanotechnologyShanghai 200240People’s Republic of China Department of Nuclear MedicineRui Jin HospitalSchool of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China Scientific Research CenterShanghai Public Health Clinical CenterFudan UniversityShanghai 201508People’s Republic of China Tongren HospitalShanghai Jiao Tong University School of Medicine1111 XianXia RoadShanghai 200336People’s Republic of China 

出 版 物：《Nano-Micro Letters》 (纳微快报（英文版）)

年 卷 期：2020年第12卷第10期

页      面：36-52页

核心收录：

学科分类：1002[医学-临床医学] 0808[工学-电气工程] 07[理学] 0809[工学-电子科学与技术（可授工学、理学学位）] 070205[理学-凝聚态物理] 0817[工学-化学工程与技术] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 10[医学] 0702[理学-物理学] 

基　　金：financially supported by National Nature Scientific foundation(81803094,81802979 and 81921002) the National Foundational Basic Research Project of China(2017YFA0205301 and 2015CB931802) Shanghai Municipal Commission of Economy and Information Technology Fund(No.XC-ZXSJ-02-2016-05) the medical engineering cross project of Shanghai Jiao Tong university(YG2017ZD05,YG2016ZD10 and YG2017Z D05) the Project of Thousand Youth Talents from China the National Key Research and Development Program of China(2017YFC1200904 and 2017YFE0124400)。 

主　　题：Human iPS MnO2@Ce6 nanoprobes Photodynamic therapy Immunotherapy Cancer 

摘      要：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(P0.05).The iPS-MnO2@Ce6 markedly inhibited tumor growth and metastasis and reduced mortality in mice models with tumor.Human iPS s loaded with MnO2-based nanoprobes are a promising strategy for simultaneous PDT and enhanced immunotherapy against tumor and own clinical translational prospect.