title: Mitochondrial electron transport chain identified as a novel molecular target of SPIO nanoparticles mediated cancer-specific cytotoxicity.
abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) are highly cytotoxic and target cancer cells with high specificity; however, the mechanism by which SPIONs induce cancer cell-specific cytotoxicity remains unclear. Herein, the molecular mechanism of SPION-induced cancer cell-specific cytotoxicity to cancer cells is clarified through DNA microarray and bioinformatics analyses. SPIONs can interference with the mitochondrial electron transport chain (METC) in cancer cells, which further affects the production of ATP, mitochondrial membrane potential, and microdistribution of calcium, and induces cell apoptosis. Additionally, SPIONs induce the formation of reactive oxygen species in mitochondria; these reactive oxygen species trigger cancer-specific cytotoxicity due to the lower antioxidative capacity of cancer cells. Moreover, the DNA microarray and gene ontology analyses revealed that SPIONs elevate the expression of metallothioneins in both normal and cancer cells but decrease the expression of METC genes in cancer cells. Overall, these results suggest that SPIONs induce cancer cell death by targeting the METC, which is helpful for designing anti-cancer nanotheranostics and evaluating the safety of future nanomedicines.
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
authors.forename: Chengyong
authors.initials: C
authors.lastname: He
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
authors.forename: Shengwei
authors.initials: S
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Microbiology and Immunology, Xiamen Medical College, Xiamen 361008, China.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
authors.forename: Gan
authors.initials: G
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China; Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: Mi
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China. Electronic address: Linych@xmu.edu.cn.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China. Electronic address: linzhn@xmu.edu.cn.
authors.forename: Zhongning
authors.initials: Z
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China. Electronic address: gangliu.cmitm@xmu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D019295:Computational Biology; D003911:Dextrans / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D063990:Gene Ontology; D056945:Hep G2 Cells; D006801:Humans; D058185:Magnetite Nanoparticles; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003911:Dextrans; D058185:Magnetite Nanoparticles; D000255:Adenosine Triphosphate; C065507:ferumoxides
keywords: Cancer cell; Cytotoxicity; Microarray; Mitochondria electron transport chain; SPIONs