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学科主题: 物理化学
题名: Elevating mitochondrial reactive oxygen species by mitochondria-targeted inhibition of superoxide dismutase with a mesoporous silica nanocarrier for cancer therapy
作者: Zhang, Yi1, 2;  Hu, Zhengyan1, 2;  Xu, Guiju1, 2;  Gao, Chuanzhou3;  Wu, Ren'an1;  Zou, Hanfa1
通讯作者: 吴仁安 ;  邹汉法
关键词: mitochondria ;  reactive oxygen species ;  apoptosis ;  mesoporous silica ;  nanoparticles ;  drug delivery
刊名: NANO RESEARCH
发表日期: 2014-08-01
DOI: 10.1007/s12274-014-0473-4
卷: 7, 期:8, 页:1103-1115
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Physical Sciences ;  Technology
类目[WOS]: Chemistry, Physical ;  Nanoscience & Nanotechnology ;  Materials Science, Multidisciplinary ;  Physics, Applied
研究领域[WOS]: Chemistry ;  Science & Technology - Other Topics ;  Materials Science ;  Physics
英文摘要: In the intrinsic pathway of apoptosis, stresses of mitochondrial reactive oxygen species (mitoROS) might be sensed as more effective signals than those in cytosol, as mitochondria are the major sources of reactive oxygen species (ROS) and pivotal components during cell apoptosis. Mitochondrial superoxide dismutase (SOD2) takes the leading role in eliminating mitoROS, and inhibition of SOD2 might induce severe disturbances overwhelming the mitochondrial oxidative equilibrium, which would elevate the intracellular oxidative stresses and drive cells to death. Herein, we report a general strategy to kill cancer cells by targeted inhibition of SOD2 using 2-methoxyestradiol (2-ME, an inhibitor for the SOD family) via a robust mitochondria-targeted mesoporous silica nanocarrier (mtMSN), with the expected elevation of mitoROS and activation of apoptosis in HeLa cells. Fe3O4@MSN was employed in the mitochondria-targeted drug delivery and selective inhibition of mitochondrial enzymes, and was shown to be stable with good biocompatibility and high loading capacity. Due to the selective inhibition of SOD2 by 2-ME/mtMSN, enhanced elevation of mitoROS (132% of that with free 2-ME) was obtained, coupled with higher efficiency in initiating cell apoptosis (395% of that with free 2-ME in 4 h). Finally, the 2-ME/mtMSN exhibited powerful efficacy in targeted killing of HeLa cells by taking advantage of both biological recognition and magnetic guiding, causing 97.0% cell death with only 2 mu g/mL 2-ME/mtMSN, hinting at its great potential in cancer therapy through manipulation of the delicate mitochondrial oxidative balance.
关键词[WOS]: DRUG-DELIVERY ;  IN-VIVO ;  CELLS ;  APOPTOSIS ;  ROS ;  NANOPARTICLES ;  THERAPEUTICS ;  ACTIVATION
语种: 英语
WOS记录号: WOS:000341172400002
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/143814
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Natl Chromatog R&A Ctr, Dalian 116023, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Dalian Med Univ, Inst Canc Stem Cell, Dalian 116044, Peoples R China

Recommended Citation:
Zhang, Yi,Hu, Zhengyan,Xu, Guiju,et al. Elevating mitochondrial reactive oxygen species by mitochondria-targeted inhibition of superoxide dismutase with a mesoporous silica nanocarrier for cancer therapy[J]. NANO RESEARCH,2014,7(8):1103-1115.
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