Translocation of silver nanoparticles in theex vivohuman placenta perfusion model characterized by single particle ICP-MS

Abstract

With the extensive use of silver nanoparticles (AgNPs) in various consumer products their potential toxicity is of great concern especially for highly sensitive population groups such as pregnant women and even the developing fetus. To understand if AgNPs are taken up and cross the human placenta, we studied their translocation and accumulation in the human ex vivo placenta perfusion model by single particle ICP-MS (spICP-MS). The impact of different surface modifications on placental transfer was assessed by AgNPs with two different modifications: polyethylene glycol (AgPEG NPs) and sodium carboxylate (AgCOONa NPs). AgNPs and ionic Ag were detected in the fetal circulation in low but not negligible amounts. Slightly higher Ag translocation across the placental barrier for perfusion with AgPEG NPs and higher AgNP accumulation in placental tissue for perfusion with AgCOONa NPs were observed. Since these AgNPs are soluble in water, we tried to distinguish between the translocation of dissolved and particulate Ag. Perfusion with AgNO3 revealed the formation of Ag containing NPs in both circulations over time, of which the amount and their size in the fetal circulation were comparable to those from perfusion experiments with both AgNP types. Although we were not able to clarify whether intact AgNPs and/or Ag precipitates from dissolved Ag cross the placental barrier, our study highlights that uptake of Ag ions and/or dissolution of AgNPs in the tissue followed by re-precipitation in the fetal circulation needs to be considered as an important pathway in studies of AgNP translocation across biological barriers.

Combination of the BeWo b30 placental transport model and the embryonic stem cell test to assess the potential developmental toxicity of silver nanoparticles

“…Exposure of the placental BeWo cell layer to 1 mg/L of (LA), (Cit), (BPEI) AgNPs, and AgNO 3 for different durations resulted in a time-dependent increase of total Ag in the cellular compartments. The transport of silver across the placental cell layer was favorable as ionic silver rather than particulate, which was similarly reported using the ex vivo human placental perfusion model where the transport of ionic silver was1 0-fold higher than that of particulates [43]. The spICP-MS measurements after 24 h exposure to the different AgNPs showed the presence of AgNPs in the cellular and basolateral compartments.…”

“…Only a small mass fraction of this silver was detected in particulate form (> 25 nm). Interestingly, the authors point out that AgNPs in the fetal circulation could originate from de novo formation following ionic Ag translocation [43]. From the limited number of in vivo studies of placental transport of NPs where pregnant animals were used, AgNPs were found to be able to cross the placental barrier of rats and reach the fetus [48][49][50][51][52].…”

Translocation of (ultra)fine particles and nanoparticles across the placenta; a systematic review on the evidence of in vitro, ex vivo, and in vivo studies

“…For example, after 6 h of perfusion, a placental accumulation of 4–7 μg/g and 2–14 μg/g was observed for 3 nm PEGylated and 4 nm carboxylated Au NPs, respectively, while the respective particle concentration in the fetal perfusate was only 0.0031 μg/mL and 0 μg/mL [ 31 ]. As observed for in vitro studies, an association between placental transfer and particle size is present; an increased placental transfer was observed for perfusions with smaller particle sizes [ 37 , 40 – 43 ]. For instance, Wick et al found that PS NPs up to 240 nm were able to cross the placenta and reach the fetal circulation already after a few minutes of perfusion, while 500 nm PS NPs were mainly retained in the placental tissue and maternal circuit [ 43 ].…”

Analysis of the Exposure of Organisms to the Action of Nanomaterials

“…The sources of nanoparticles found in the digestive system are medicines and medicinal substances, but also food products stored in packaging modified with nanoparticles. Due to the antimicrobial activity of AgNPs, they also began to be used as an additive to materials in contact with food, including kitchen utensils and storage containers [136]. Manufacturing products modified with nanoparticles intended for food processing and storage without tests verifying their non-toxicity, the degree of their accumulation in cells and the percentage of penetration of nanoparticles into food, is risky [85].…”