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Gold nanoparticles (GNPs) have considerable applications in biomedicine, such as in bio-sensing, bio-imaging, drug delivery and photothermal therapeutics. However, currently there are limited information regarding the impact of pregnancy on their biodistribution, elimination and toxicity. In this study, we investigated the biodistribution and potential toxic effects of different-sized GNPs (1.5, 4.5, 13, 30 and 70 nm in diameter) in non-pregnant and pregnant mice at different gestational ages (E5.5, 7.5, 9.5, 11.5 and 13.5). 5h after intravenous injection, GNPs exhibited size-dependent biodistribution profiles; however, regardless of size, no significant biodistribution changes were observed between non-pregnant and pregnant mice. Kinetic studies showed that 4.5 nm GNPs were primarily excreted through urine within 5h, whereas 30 nm GNPs had a more prolonged blood circulation time. No apparent toxic effects (e.g., increased mortality, altered behavior, reduced animal weight, abnormal organ morphology or reduced pregnancy duration) were observed with different-sized GNPs in pregnant mice. However, treatment with 30 nm GNPs induced mild emphysema-like changes in lungs of pregnant mice. These results indicated that the maternal biodistribution patterns of GNPs in pregnant mice depended on particle size, but not gestational age; organ-specific adverse effects may arise with treatment with some GNPs according to their size., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The materno-fetal transfer of nanoparticles is a critical issue in designing theranoustic nanoparticles for in vivo applications during pregnancy. Recent studies have reported that certain nanoparticles can cross the placental barrier in healthy pregnant animals depending on the size and surface modification of the nanoparticles and the developmental stages of the fetuses. However, materno-fetal transfer under pathological pregnant conditions has not been examined so far. Here, it is shown that intrauterine inflammation can enhance the materno-fetal transfer of nanoparticles in the late gestation stage of murine pregnancy in a size-dependent manner. Three different-sized gold nanoparticles (Au NPs) with diameters of 3 (Au3), 13 (Au13) and 32 (Au32) nm are applied. The accumulation of Au3 and Au13 nanoparticles in the fetuses is significantly increased in intrauterine inflammatory mice compared with healthy control mice: the concentration of Au3 is much higher than Au13 in fetal tissues of intrauterine inflammatory mice. In contrast, Au32 nanoparticles cannot cross the placental barrier either in healthy or in intrauterine inflammatory mice. The possible underlying mechanism of the increased materno-fetal transfer of small-sized nanoparticles on pathological conditions is inferred to be the structural and functional abnormalities of the placenta under intrauterine inflammation. The size of the nanoparticles is one of the critical factors which determines the extent of fetal exposure to nanoparticles in murine pregnancy under inflammatory conditions., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nanoparticle exposure in pregnancy may result in placental damage and fetotoxicity; however, the factors that determine fetal nanoparticle exposure are unclear. Here we have assessed the effect of gestational age and nanoparticle composition on fetal accumulation of maternally-administered nanomaterials in mice. We determined the placental and fetal uptake of 13 nm gold nanoparticles with different surface modifications (ferritin, PEG and citrate) following intravenous administration at E5.5-15.5. We showed that prior to E11.5, all tested nanoparticles could be visualized and detected in fetal tissues in significant amounts; however, fetal gold levels declined dramatically post-E11.5. In contrast, Au-nanoparticle accumulation in the extraembryonic tissues (EET) increased 6-15 fold with gestational age. Fetal and EET accumulation of ferritin- and PEG-modified nanoparticles was considerably greater than citrate-capped nanoparticles. No signs of toxicity were observed. Fetal exposure to nanoparticles in murine pregnancy is, therefore, influenced by both stage of embryonic/placental maturation and nanoparticle surface composition.