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学科主题物理化学
Elevating mitochondrial reactive oxygen species by mitochondria-targeted inhibition of superoxide dismutase with a mesoporous silica nanocarrier for cancer therapy
Zhang, Yi1,2; Hu, Zhengyan1,2; Xu, Guiju1,2; Gao, Chuanzhou3; Wu, Ren'an1; Zou, Hanfa1; Wu RA(吴仁安); Zou HF(邹汉法)
关键词Mitochondria Reactive Oxygen Species Apoptosis Mesoporous Silica Nanoparticles Drug Delivery
刊名NANO RESEARCH
2014-08-01
DOI10.1007/s12274-014-0473-4
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
关键词[WOS]DRUG-DELIVERY ; IN-VIVO ; CELLS ; APOPTOSIS ; ROS ; NANOPARTICLES ; THERAPEUTICS ; ACTIVATION
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.
语种英语
WOS记录号WOS:000341172400002
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/143814
专题中国科学院大连化学物理研究所
通讯作者Wu RA(吴仁安); Zou HF(邹汉法)
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
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GB/T 7714
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.
APA Zhang, Yi.,Hu, Zhengyan.,Xu, Guiju.,Gao, Chuanzhou.,Wu, Ren'an.,...&邹汉法.(2014).Elevating mitochondrial reactive oxygen species by mitochondria-targeted inhibition of superoxide dismutase with a mesoporous silica nanocarrier for cancer therapy.NANO RESEARCH,7(8),1103-1115.
MLA Zhang, Yi,et al."Elevating mitochondrial reactive oxygen species by mitochondria-targeted inhibition of superoxide dismutase with a mesoporous silica nanocarrier for cancer therapy".NANO RESEARCH 7.8(2014):1103-1115.
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