title: Evaluation of multiwalled carbon nanotube cytotoxicity in cultures of human brain microvascular endothelial cells grown on plastic or basement membrane.
abstract: There is a growing interest in the use of multiwalled carbon nanotubes (MWCNTs) to treat diseases of the brain. Little is known about the effects of MWCNTs on human brain microvascular endothelial cells (HBMECs), which make up the blood vessels in the brain. In our studies, we evaluate the cytotoxicity of MWCNTs and acid oxidized MWNCTs, with or without a phospholipid-polyethylene glycol coating. We determined the cytotoxic effects of MWCNTs on both tissue-mimicking cultures of HBMECs grown on basement membrane and on monolayer cultures of HBMECs grown on plastic. We also evaluated the effects of MWCNT exposure on the capacity of HBMECs to form rings after plating on basement membrane, a commonly used assay to evaluate angiogenesis. We show that tissue-mimicking cultures of HBMECs are less sensitive to all types of MWCNTs than monolayer cultures of HBMECs. Furthermore, we found that MWCNTs have little impact on the capacity of HBMECs to form rings. Our results indicate that relative cytotoxicity of MWCNTs is significantly affected by the type of cell culture model used for testing, and supports further research into the use of tissue-mimicking endothelial cell culture models to help bridge the gap between in vitro and in vivo toxicology.
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC 27157, USA.
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Eldridge
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC 27157, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Xing
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC 27157, USA.
authors.forename: Cale D
authors.initials: CD
authors.lastname: Fahrenholtz
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC 27157, USA; Comprehensive Cancer Center of Wake Forest School of Medicine, Winston Salem, NC 27157, USA. Electronic address: rasingh@wakehealth.edu.
authors.forename: Ravi N
authors.initials: RN
authors.lastname: Singh
mesh_terms: D001485:Basement Membrane; D001921:Brain / Q000166:cytology; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D055806:Microvessels / Q000166:cytology; D037742:Nanotubes, Carbon / Q000633:toxicity*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010969:Plastics
chemical_list: D037742:Nanotubes, Carbon; D010969:Plastics
keywords: Angiogenesis; Blood brain barrier; Extracellular matrix; Nanoparticle; Toxicity