title: Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice.
abstract: BACKGROUND
  Single wall carbon nanotubes (SWCNTs) are considered promising nanoparticles for industrial and biomedical applications; however their potential toxicity in several biological systems, including the feto-placental unit, has been demonstrated. Functionalization of SWCNTs with polyethylene glycol chains (PEG-SWCNTs) dramatically reduces their toxicity, and for this reason PEG-SWCNTs are candidates for biomedical applications. However, no data are available on their safety for the developing embryo, in spite of the clinical and social relevance of this topic. The purpose of this study is therefore to investigate the safety of PEG-SWCNTs for their use as biomedical carriers in pregnancy.
  
  
  METHODS
  For toxicological studies, amino-functionalized PEG-SWCNT were intravenously injected in CD1 pregnant mice at different doses (range 0.1-30 μg/mouse), in single or multiple administrations. For biodistribution studies, fluorescently labeled PEG-SWCNTs were obtained by acylation of terminal PEG amino groups with near infrared emitting fluorochromes (PEG-SWCNT-750) and injected at the dosage of 10 μg/mouse, at either day 5.5 (when the placenta is still developing) or day 14.5 of gestation (when the maturation of the placenta is complete).
  
  
  RESULTS
  We found no adverse effects both on embryos and dams up to the dose of 10 μg/mouse. At the dose of 30 μg/mouse, occasional teratogenic effects, associated with placental damage, were detected both when administered as a single bolus (1 out of 10 dams; 1 malformed embryo) or as multiple doses (2 out of 10 dams; 5 malformed embryos). The difference in the prevalence of dams with malformed embryos between the 30 μg exposed group and controls approached the statistical significance (p = 0.06). Hepatic damage in dams was seen only in the multiple exposure group (4 out of 10; p = 0.04 when compared with the single exposure group or controls). PEG-SWCNT-750 reached the conceptus when administered early in pregnancy. At later stages, PEG-SWCNT-750 were detected in the placenta and the yolk sac, but not in the embryo.
  
  
  CONCLUSIONS
  PEG-SWCNTs may cause occasional teratogenic effects in mice beyond a threshold dose. Such effect might depend on their ability to reach the feto-placenta unit. Although not automatically transferable to humans, these data should be considered if exposing women during pregnancy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Campagnolo
authors.forename: Micol
authors.initials: M
authors.lastname: Massimiani
authors.forename: Graziana
authors.initials: G
authors.lastname: Palmieri
authors.forename: Roberta
authors.initials: R
authors.lastname: Bernardini
authors.forename: Cristiano
authors.initials: C
authors.lastname: Sacchetti
authors.forename: Antonio
authors.initials: A
authors.lastname: Bergamaschi
authors.forename: Lucia
authors.initials: L
authors.lastname: Vecchione
authors.forename: Andrea
authors.initials: A
authors.lastname: Magrini
authors.forename: Massimo
authors.initials: M
authors.lastname: Bottini
authors.forename: Antonio
authors.initials: A
authors.lastname: Pietroiusti
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D007275:Injections, Intravenous; D008163:Luminescent Measurements; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D037742:Nanotubes, Carbon / Q000633:toxicity*; D061848:Optical Imaging; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000633:toxicity*; D011247:Pregnancy; D018570:Risk Assessment; D014018:Tissue Distribution; D051598:Whole Body Imaging
chemical_list: D037742:Nanotubes, Carbon; D011092:Polyethylene Glycols