Abstract
BackgroundSingle 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.MethodsFor 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).ResultsWe 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.ConclusionsPEG-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.
Highlights
Since their discovery, almost 20 years ago, carbon nanotubes (CNTs), a class of fiber-shaped nanoparticles (NPs), have been indicated as good candidates for many applications in industrial and biomedical settings
Production and characterization of polyethylene glycol (PEG)-single wall CNTs (SWCNTs) Individual amino-functionalized PEGSWCNTs were fabricated from the processing of commercially available single SWCNTs through a non-covalent protocol based on the adsorption onto SWCNT sidewalls of phospholipids modified with PEG chains, carrying amino groups at their end
Phospholipids bind strongly to SWCNTs through hydrophobic interactions between the fatty acid aliphatic chains and the graphitic sidewalls, leaving the hydrophilic PEG chains protruding from the sidewall [13]
Summary
Almost 20 years ago, carbon nanotubes (CNTs), a class of fiber-shaped nanoparticles (NPs), have been indicated as good candidates for many applications in industrial and biomedical settings For such reason, their biocompatibility has been extensively investigated over the last 10 years, and evidences that CNTs might have negative effects in biological systems have induce toxicity by locally interfering with placental functions. No data are currently available on the effects of PEG-SWCNT exposure during pregnancy in dams and embryos This matter is relevant, for the obvious clinical and social implications, and in light of the high sensitivity of embryonic tissues to the toxic effects of CNTs, which induce severe embryo abnormalities at doses having no toxic effects on maternal organs [4]. The purpose of this study is to investigate the safety of PEG-SWCNTs for their use as biomedical carriers in pregnancy
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