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 cyto...

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Bibliographic Details
Published in:Biomaterials 2016-03, Vol.83, p.102-114
Main Authors: He, Chengyong, Jiang, Shengwei, Jin, Haijing, Chen, Shuzhen, Lin, Gan, Yao, Huan, Wang, Xiaoyong, Mi, Peng, Ji, Zhiliang, Lin, Yuchun, Lin, Zhongning, Liu, Gang
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Advanced Basic Science
Antioxidants - pharmacology
Cancer
Cancer cell
Cell Death - drug effects
Chains
Computational Biology
Cytotoxicity
Dentistry
Deoxyribonucleic acid
Dextrans - pharmacology
Electron transport
Electron Transport - drug effects
Endocytosis - drug effects
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic - drug effects
Gene Ontology
Genes
Hep G2 Cells
Humans
Magnetite Nanoparticles
Microarray
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondria electron transport chain
Molecular Targeted Therapy
Nanoparticles
Nanoparticles - chemistry
Nanoparticles - ultrastructure
Nanostructure
Neoplasms - metabolism
Neoplasms - pathology
Oligonucleotide Array Sequence Analysis
Signal Transduction - drug effects
SPIONs
Subcellular Fractions - drug effects
Subcellular Fractions - metabolism
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2016.01.010