Structure-Dependent Mitochondrial Dysfunction and Hypoxia Induced with Single-Walled Carbon Nanotu

Structure-Dependent Mitochondrial Dysfunction and Hypoxia Induced with Single-Walled Carbon Nanotubes

Carbon Nanotubes

tructure-Dependent Mitochondrial Dysfunction and S

Hypoxia Induced with Single-Walled Carbon Nanotubes

Li-RongWang,XueXue,Xiao-MeiHu,Ming-YuanWei,Chun-QiuZhang,Guang-LuGe,*andXing-JieLiang*size, shape, surface chemistry and other physicochemical properties. Exposure to a well-characterized subpopulation of speci c nanomaterials is therefore desired to reveal more detailed mechanisms. This study develops scalable density gradient ultracentrifugation sorting of highly dispersed single-walled carbon nanotubes (SWNTs) into four distinct bands based on diameter, aggregation and structural integrity, with greatly improved ef ciency, yield, and reproducibility. With guarantee of high yield and stability of four SWNT fractions, we could, for the rst time, investigate the structure-dependent bioeffects of four SWNT fractions. Among these, singly-dispersed integral SWNTs showed no signi cant effects on the mitochondrial functions and hypoxia. The aggregated integral SWNTs showed more signi cant effects on the mitochondrial dysfunction and hypoxia compared to the aggregated SWNTs with poor structure integrity. Then, it was found that the aggregated integral SWNTs induced the irregular mitochondria respiratory and pro-apoptotic proteins activation, while aggregated SWNTs with poor structure integrity greatly enhanced reactive oxygen species (ROS) levels. This work supports the view that control of the distinct structure characteristics of SWNTs helps establish clearer structure-bioeffect correlation and health risk assessment. It is also hoped that these results can help in the design of nanomaterials with higher ef ciency and accuracy in subcellular translocation.

Cytotoxicity of nanomaterials on living systems is known to be affected by their

Dr.L.-R.Wang[+] , Prof. G.-L. Ge,

Chinese Academy of Sciences Key Laboratory

of Standardization and Measurement for Nanotechnology

National Center for Nanoscience

and Technology of China Beijing 100190 ,China E-mail:gegl@nanoctr.cnDr. X. Xue,[+] X.-M. Hu, C.-Q. Zhang, Prof. X.-J. Liang

Chinese Academy of Sciences Key Laboratory

for Biological Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology of China

Beijing 100190 ,China E-mail:liangxj@nanoctr.cnDr.M.-Y.WeiDepartment of Bioengineering

University of Texas at Arlington

500 UTA Blvd ,Arlington ,TX 76010 ,U.S.A

[+] These authors contributed equally to this work.

1.Introduction esearch on single-walled carbon nanotubes (SWNTs) R

has been pursued extensively in the past few decades, due to their unique electrical, optical, and mechanical proper-[ 1,2 ] including nanoelectronics, [ 3] ties and wide applications

[ 4] biomolecular recognition devices, [ 5,6 ]mole-biosensors,

[ 7] and cancer therapy. [ 8,9 ]The biological cular transporters,

[ 10,11 ]but effects of carbon nanotubes have been studied,

showed controversial results due to heterogeneity in their intrinsic properties, including size, surface chemistry, chirality,

[ 12 ] chemical composition, and etc. For example, Sayes et al.

reported that the functionalization differences could reduce

[ 13 ]showed the SWNT cytotoxicity, while Dumortier et al.

that there were no obvious effects of functionalized carbon nanotubes on immune cells. As a result, the critical factors of SWNT inherent structure that determine cell behaviors remained elusive. Meanwhile, as the biological effects of SWNTs, previous studies have demonstrated that mitochon-wileyonlinelibrary.com

DOI: 10.1002/smll.201303342

small 2014,

DOI: 10.1002/smll.201303342

© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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