title: Structure-dependent mitochondrial dysfunction and hypoxia induced with single-walled carbon nanotubes.
abstract: Cytotoxicity of nanomaterials on living systems is known to be affected by their size, shape, surface chemistry, and other physicochemical properties. Exposure to a well-characterized subpopulation of specific 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 efficiency, yield, and reproducibility. With guarantee of high yield and stability of four SWNT fractions, it is possible for the first time, to investigate the structure-dependent bioeffects of four SWNT fractions. it is possible Among these, singly-dispersed integral SWNTs show no significant effects on the mitochondrial functions and hypoxia. The aggregated integral SWNTs show more significant effects on the mitochondrial dysfunction and hypoxia compared to the aggregated SWNTs with poor structure integrity. Then, it is 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 efficiency and accuracy in subcellular translocation.
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Standardization and Measurement for Nanotechnology, National Center for Nanoscience and Technology of China, Beijing, 100190, China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Wang
authors.forename: Xue
authors.initials: X
authors.lastname: Xue
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Hu
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Wei
authors.forename: Chun-Qiu
authors.initials: CQ
authors.lastname: Zhang
authors.forename: Guang-Lu
authors.initials: GL
authors.lastname: Ge
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D006801:Humans; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013059:Spectrum Analysis, Raman
chemical_list: D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species
keywords: hypoxia; mitochondrial dysfunction; single-walled carbon nanotubes; structure-dependent