摘要：Background: Nanoparticle exposure in utero might not be a major concern yet, but it could become more important with the increasing application of nanomaterials in consumer and medical products. Several epidemiologic and in vitro studies have shown that nanoparticles can have potential toxic effects. However, nanoparticles also offer the opportunity to develop new therapeutic strategies to treat specifically either the pregnant mother or the fetus. Previous studies mainly addressed whether nanoparticles are able to cross the placental barrier. However, the transport mechanisms underlying nanoparticle translocation across the placenta are still unknown. Objectives: In this study we examined which transport mechanisms underlie the placental transfer of nanoparticles.Methods: We used the ex vivo human placental perfusion model to analyze the bidirectional transfer of plain and carboxylate modified polystyrene particles in a size range between 50 and 300 nm. Results: We observed that the transport of polystyrene particles in the fetal to maternal direction was significantly higher than for the maternal to fetal direction. Regardless of their ability to cross the placental barrier and the direction of perfusion, all polystyrene particles accumulated in the syncytiotrophoblast of the placental tissue.Conclusions: Our results indicate that the syncytiotrophoblast is the key player in regulating nanoparticle transport across the human placenta. The main mechanism underlying this translocation is not based on passive diffusion, but is likely to involve an active, energy-dependent transport pathway. These findings will be important for reproductive toxicology as well as for pharmaceutical engineering of new drug carriers.Citation: Grafmueller S, Manser P, Diener L, Diener PA, Maeder-Althaus X, Maurizi L, Jochum W, Krug HF, Buerki-Thurnherr T, von Mandach U, Wick P. 2015. Bidirectional transfer study of polystyrene nanoparticles across the placental barrier in an ex vivo human placental perfusion model. Environ Health Perspect 123:1280–1286; http://dx.doi.org/10.1289/ehp.1409271 Address correspondence to P. Wick, Empa, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Particles-Biology Interactions, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland. Telephone: 41 58 765 76 84. E-mail: peter.wick@empa.chWe thank M. Roesslein for technical support in measurement of particle size distribution.This work was financially supported by the Swiss National Foundation (NRP 64 Program, grant 4064-131232). This project has received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under grant agreement no. 263215 (MARINA) and no. 309329 (NANOSOLUTIONS).The authors declare they have no actual or potential competing financial interests.Received: 29 September 2014Accepted: 5 May 2015Advance Publication: 8 May 2015Final Publication: 1 December 2015 Note to readers with disabilities: EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact ehp508@niehs.nih.gov. Our staff will work with you to assess and meet your accessibility needs within 3 working days. Supplemental Material PDF (6.9 MB)--------------------------------------------------------------------------------Note to readers with disabilities: EHP has provided a 508-conformant table of contents summarizing the Supplemental Material for this article (see below) so readers with disabilities may determine whether they wish to access the full, nonconformant Supplemental Material. If you need assistance accessing this or any other content on this site, please contact ehp508@niehs.nih.gov. Our staff will work with you to assess and meet your accessibility needs within 3 working days. Supplemental Table of Contents PDF (119 KB)
