title: Superparamagnetic core/shell GoldMag nanoparticles: size-, concentration- and time-dependent cellular nanotoxicity on human umbilical vein endothelial cells and the suitable conditions for magnetic resonance imaging.
abstract: BACKGROUND
  GoldMag nanoparticles (GMNPs) possess the properties of colloid gold and superparamagnetic iron oxide nanoparticles, which make them useful for delivery, separation and molecular imaging. However, because of the nanometer effect, GMNPs are highly toxic. Thus, the biosafety of GMNPs should be fully studied prior to their use in biomedicine. The main purpose of this study was to evaluate the nanotoxicity of GMNPs on human umbilical vein endothelial cells (HUVECs) and determine a suitable size, concentration and time for magnetic resonance imaging (MRI).
  
  
  RESULTS
  Transmission electron microscopy showed that GMNPs had a typical shell/core structure, and the shell was confirmed to be gold using energy dispersive spectrometer analysis. The average sizes of the 30 and 50 nm GMNPs were 30.65 ± 3.15 and 49.23 ± 5.01 nm, respectively, and the shell thickness were 6.8 ± 0.65 and 8.5 ± 1.36 nm, respectively. Dynamic light scattering showed that the hydrodynamic diameter of the 30 and 50 nm GMNPs were 33.2 ± 2.68 and 53.12 ± 4.56 nm, respectively. The r 2 relaxivity of the 50 nm GMNPs was 98.65 mM(-1) s(-1), whereas it was 80.18 mM(-1) s(-1) for the 30 nm GMNPs. The proliferation, cytoskeleton, migration, tube formation, apoptosis and ROS generation of labeled HUVECs depended on the size and concentration of GMNPs and the time of exposure. Because of the higher labeling rate, the 50 nm GMNPs exhibited a significant increase in nanotoxicity compared with the 30 nm GMNPs at the same concentration and time. At no more than 25 μg/mL and 12 hours, the 50 nm GMNPs exhibited no significant nanotoxicity in HUVECs, whereas no toxicity was observed at 50 μg/mL and 24 hours for the 30 nm GMNPs.
  
  
  CONCLUSIONS
  These results demonstrated that the nanotoxicity of GMNPs in HUVECs depended on size, concentration and time. Exposure to larger GMNPs with a higher concentration for a longer period of time resulted in a higher labeling rate and ROS level for HUVECs. Coupled with r 2 relaxivity, it was suggested that the 50 nm GMNPs are more suitable for HUVEC labeling and MRI, and the suitable concentration and time were 25 μg/mL and 12 hours.
authors.affiliation: Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. hummer198625@163.com.
authors.forename: Mingfu
authors.initials: M
authors.lastname: Gong
authors.affiliation: Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. cqxqyyyh@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. cqxqyyzs@163.com.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. cqxqyyyy@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. cqxqyyzd@163.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. cqxqyyqyy@163.com.
authors.forename: Yueyong
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. cqxqyyzlg@163.com.
authors.forename: Liguang
authors.initials: L
authors.lastname: Zou
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006046:Gold / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000633:toxicity; D046529:Microscopy, Electron, Transmission; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; D006046:Gold; C065507:ferumoxides