The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes

The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes
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DOI:
10.1016/j.biomaterials.2007.09.002
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发表时间:
2007-12-01
期刊:
影响因子:
14
通讯作者:
Trajkovic, Vladimir
Trajkovic, Vladimir
中科院分区:
工程技术1区
文献类型:
--
作者:
Markovic, Zoran;Todorovic-Markovic, Biljana;Trajkovic, Vladimir

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由于在某些条件下诱导细胞死亡的能力,富勒烯(C-60)是潜在的抗癌剂和毒性剂。纳米C-60(nano-C-60,nC(60))的胶体悬浮液具有极强的毒性,但其细胞毒性机制尚未完全了解。通过结合实验分析和数学建模,我们研究了不同nC(60)悬浮液的活性氧(ROS)介导的细胞毒性的要求,所述悬浮液通过在四氢呋喃(THF/nC(60))和乙醇(EtOH/nC(60))中的溶剂交换法或通过在水中的延长混合(aqu/nC(60))制备。关于它们产生ROS和引起线粒体去极化随后坏死细胞死亡的能力,nC(60)悬浮液按以下顺序排列:THF/nC(60)> EtOH/nC(60)>aqu/nC(60)。单线态氧(O-1(2))产生的数学模型表明,嵌入富勒烯晶体中的溶剂的O-1(2)-猝灭能力(THF/nC(60)< EtOH/nC(60)< aqU/nC(60))决定了它们产生ROS并引起细胞损伤的能力。这些数据可以。对胶体富勒烯的毒理学和生物医学应用具有重要意义。(C)2007爱思唯尔有限公司版权所有。
Because of the ability to induce cell death in certain conditions, the fullerenes (C-60) are potential anticancer and toxic agents. The colloidal suspension of crystalline C-60 (nano-C-60, nC(60)) is extremely toxic, but the mechanisms of its cytotoxicity are not completely understood. By combining experimental analysis and mathematical modelling, we investigate the requirements for the reactive oxygen species (ROS)-mediated cytotoxicity of different nC(60) suspensions, prepared by solvent exchange method in tetrahydrofuran (THF/nC(60)) and ethanol (EtOH/nC(60)), or by extended mixing in water (aqu/nC(60)). With regard to their capacity to generate ROS and cause mitochondrial depolarization followed by necrotic cell death, the nC(60) suspensions are ranked in the following order: THF/nC(60) > EtOH/nC(60)>aqu/nC(60). Mathematical modelling of singlet oxygen (O-1(2)) generation indicates that the O-1(2)-quenching power (THF/nC(60) < EtOH/nC(60) < aqU/nC(60)) of the solvent intercalated in the fullerene crystals determines their ability to produce ROS and cause cell damage. These data could. have important implications for toxicology and biomedical application of colloidal fullerenes. (C) 2007 Elsevier Ltd. All rights reserved.