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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.