Research on nanoparticles in human perfused placenta: State of the art and perspectives

Increasing human exposure to nanoparticles (NPs) from various sources raises concerns for public health, especially for vulnerable risk groups like pregnant women and their developing fetuses. However, nanomedicine and the prospect of creating safe and effective NP-based formulations of drugs hold great promise to revolutionize treatment during pregnancy. With maternal and fetal health at stake, risks and opportunities of NPs in pregnancy need to be carefully investigated. Importantly, a comprehensive understanding of NP transport and effects at the placenta is urgently needed considering the central position of the placenta at the maternal-fetal interface and its many essential functions to enable successful pregnancy. The perfusion of human placental tissue provides a great opportunity to achieve predictive human relevant insights, circumventing uncertainties due to considerable differences in placental structure and function across species. Here, we have reviewed the current literature on the ex vivo human placenta perfusion of NPs. From 16 available studies, it was evident that placental uptake and transfer of NPs are highly dependent on their characteristics like size and surface modifications, which is in line with previous observations from in vitro and animal transport studies. These studies further revealed that special considerations apply for the perfusion of NPs and we identified relevant controls that should be implemented in future perfusion studies. While current studies mostly focused on placental transfer of NPs to conclude on potential fetal exposure, the ex vivo placental perfusion model has considerable potential to reveal novel insights on NP effects on placental tissue functionality and signaling that could indirectly affect maternal-fetal health.