Lysosome-mitochondria-mediated apoptosis specifically evoked in cancer cells induced by gold nanorods.
Lysosome-mitochondria-mediated apoptosis specifically evoked in cancer cells induced by gold nanorods.
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DOI：
10.2217/nnm-2016-0139
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发表时间：
2016-06
期刊：
影响因子：
5.5
通讯作者：
Fulei Zhang;Xiandi Zhu;Jing Gong;Yun Sun;Di Chen;Jie Wang;Ying Wang;M. Guo;Wei Li
中科院分区：
文献类型：
--
作者：
Fulei Zhang;Xiandi Zhu;Jing Gong;Yun Sun;Di Chen;Jie Wang;Ying Wang;M. Guo;Wei Li
目的探讨金纳米棒特异性诱导肿瘤细胞凋亡的机制。材料与方法合成并优化GNRs，系统评价与细胞凋亡相关的溶酶体损伤、组织蛋白酶D、线粒体膜电位、caspase-9、切割型caspase-9、caspase-3以及GNRs在细胞内的定位。结果GNRs特异性诱导癌细胞凋亡，而对正常细胞的影响可以忽略不计。组织蛋白酶D显示，GNRs作用后，癌细胞溶酶体通透性明显高于正常细胞，线粒体膜电位明显降低。Western blot分析进一步证实线粒体损伤后通过caspase-9和caspase-3激活发生凋亡。透射电子显微镜观察显示，GNRs在大部分受损的线粒体中没有出现，而主要聚集在溶酶体中。结论GNR通过影响溶酶体和线粒体特异性地诱导癌细胞凋亡。
AIM The main aim of this article is to explain the apoptosis mechanisms of cancer cells specifically triggered by gold nanorods (GNRs). MATERIALS & METHODS GNRs were synthesized and optimized, the lysosome damage, cathepsin D, mitochondrial membrane potential, caspase-9, cleaved caspase-9, caspase-3 and intracellular GNRs location related to apoptosis was systematically evaluated. RESULTS GNRs specifically induce cancer cell apoptosis while posing a negligible impact on normal cells. After incubation with GNRs, the lysosomal permeability in cancer cells as indicated by cathepsin D was markedly higher than that in normal cells and resulted in an obvious decrease in mitochondrial membrane potential. Western blot analysis further confirmed that apoptosis occurred through caspase-9 and caspase-3 activation following mitochondrial damage. Transmission electron microscope images showed that GNRs did not appear in most of the damaged mitochondria but mainly accumulated in lysosomes. CONCLUSION These findings indicated that GNR-induced apoptosis specifically in cancer cells by affecting lysosomes and mitochondria.