单位：[1]Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430015,P. R. China.外科学系华中科技大学同济医学院附属同济医院骨科[2]Department of Obstetrics and Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430015,P. R. China.华中科技大学同济医学院附属同济医院妇产科学系妇产科教研室[3]Non-power Nuclear Technology Collaborative Innovation Center, School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning 437100, P. R. China.[4]State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, P.R. China.[5]Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) & Xi'an Institute of Biomedical Materials and Engineering (IBME), Northwestern Polytechnical University, Xi'an 710072, P. R. China.[6]State Key Laboratory of Structure Analysis for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian 116024, P. R. China.[7]Department of Epidemiology and Biostatistics, University of California, San Francisco ,California94199, United States.[8]Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.[9]State Key Laboratory of Separation Membrane and Membrane Process, School of Chemistry and Chemical Engineering & School of Environmental Science and Engineering, Tiangong University, Tianjin 300387, China.
Ferroptosis is characterized by iron accumulation and lipid peroxidation. However, a clinical dose of Fe3O4 nanoparticles could not cause effective ferroptosis in tumors, and the mechanism is yet to be completely understood. In this study, using RNA-seq data, we found that tumor cells could feedback-activate the antioxidant system by upregulating Nrf-2 expression, thus avoiding ferroptosis caused by Fe3O4 nanoparticles. We also found that DHJS (a probe for ROS generation) can antagonize Nrf-2 expression when it synergizes with Fe3O4 nanoparticles, thus inducing ferroptosis in tumor cells. Considering these findings, we created a biomimetic hybrid cell membrane camouflaged by PLGA-loaded Fe3O4 and DHJS to treat osteosarcoma. The hybrid cell membrane endowed the core nanoparticle with the extension of blood circulation life and enhanced homologous targeting ability. In addition, DHJS and Fe3O4 in nanoparticles prompted synergistically lethal ferroptosis in cancer cells and induced macrophage M1 polarization as well as the infiltration of CD8(+) T cells and dendritic cells in tumors. In summary, this study provides novel mechanistic insights and practical strategies for ferroptosis induction of Fe3O4 nanoparticles. Meanwhile, the synthesized biomimetic nanoparticles exhibited synergistic ferroptosis/immunotherapy against osteosarcoma.
基金：
This work was supported by grants from the National Nature
Science Foundation of China (82072500 and 81974351), and
Science and Technology Plans of Tianjin (22ZYJDSS00070)
第一作者单位：[1]Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430015,P. R. China.
通讯作者：
通讯机构：[3]Non-power Nuclear Technology Collaborative Innovation Center, School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning 437100, P. R. China.[9]State Key Laboratory of Separation Membrane and Membrane Process, School of Chemistry and Chemical Engineering & School of Environmental Science and Engineering, Tiangong University, Tianjin 300387, China.
推荐引用方式(GB/T 7714)：
Yu Kaixu,Chen Ying,Zhang Lu,et al.Cancer-Erythrocyte Membrane-Mimicking Fe3O4 Nanoparticles and DHJS for Ferroptosis/Immunotherapy Synergism in Tumors[J].ACS APPLIED MATERIALS & INTERFACES.2023,15(38):44689-44710.doi:10.1021/acsami.3c07379.
APA：
Yu Kaixu,Chen Ying,Zhang Lu,Zheng Yongqiang,Chen Jinlin...&Li Feng.(2023).Cancer-Erythrocyte Membrane-Mimicking Fe3O4 Nanoparticles and DHJS for Ferroptosis/Immunotherapy Synergism in Tumors.ACS APPLIED MATERIALS & INTERFACES,15,(38)
MLA：
Yu Kaixu,et al."Cancer-Erythrocyte Membrane-Mimicking Fe3O4 Nanoparticles and DHJS for Ferroptosis/Immunotherapy Synergism in Tumors".ACS APPLIED MATERIALS & INTERFACES 15..38(2023):44689-44710
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