Mitochondrial electron transport chain identified as a novel molecular target of SPIO nanoparticles mediated cancer-specific cytotoxicity
Mitochondrial electron transport chain identified as a novel molecular target of SPIO nanoparticles mediated cancer-specific cytotoxicity
复制标题
线粒体电子传递链被确定为 SPIO 纳米粒子介导的癌症特异性细胞毒性的新分子靶点
DOI：
10.1016/j.biomaterials.2016.01.010
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发表时间：
2016-03-01
期刊：
影响因子：
14
通讯作者：
Liu, Gang
中科院分区：
文献类型：
--
作者：
He, Chengyong;Jiang, Shengwei;Liu, Gang
超顺磁性氧化铁纳米颗粒（SPION）具有高度细胞毒性，并以高度特异性靶向癌细胞;然而，SPION诱导癌细胞特异性细胞毒性的机制仍不清楚。在此，通过DNA微阵列和生物信息学分析阐明了SPION诱导的癌细胞特异性细胞毒性对癌细胞的分子机制。SPION可以干扰癌细胞中的线粒体电子传递链（METC），从而进一步影响ATP的产生、线粒体膜电位和钙的微分布，并诱导细胞凋亡。此外，SPION诱导线粒体中活性氧的形成;由于癌细胞的抗氧化能力较低，这些活性氧引发癌症特异性细胞毒性。此外，DNA微阵列和基因本体分析显示SPION在正常细胞和癌细胞中均提高金属硫蛋白的表达，但在癌细胞中降低METC基因的表达。总体而言，这些结果表明SPION通过靶向METC诱导癌细胞死亡，这有助于设计抗癌纳米治疗药物和评估未来纳米药物的安全性。(C)2016爱思唯尔有限公司版权所有
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. (C) 2016 Elsevier Ltd. All rights reserved.