Transfer studies of polystyrene nanoparticles in theex vivohuman placenta perfusion model: key sources of artifacts

Abstract

Nanotechnology is a rapidly expanding and highly promising new technology with many different fields of application. Consequently, the investigation of engineered nanoparticles in biological systems is steadily increasing. Questions about the safety of such engineered nanoparticles are very important and the most critical subject with regard to the penetration of biological barriers allowing particle distribution throughout the human body. Such translocation studies are technically challenging and many issues have to be considered to obtain meaningful and comparable results. Here we report on the transfer of polystyrene nanoparticles across the human placenta using an ex vivo human placenta perfusion model. We provide an overview of several challenges that can potentially occur in any translocation study in relation to particle size distribution, functionalization and stability of labels. In conclusion, a careful assessment of nanoparticle properties in a physiologically relevant milieu is as challenging and important as the actual study of nanoparticle–cell interactions itself.

Nanopolystyrene Translocation and Fetal Deposition After Acute Lung Exposure During Late-Stage Pregnancy

“…Upon further study utilizing the ex vivo human placental perfusion model, the authors identi ed a bidirectional, size-dependent transfer of nanopolystyrene beads without cytotoxicity [20]. While it is recognized that the concentration of particles that translocate from the primary site of exposure to the fetal compartment and tissues is low [30] and that this methodology is not without limitation [31]; it is likely that nanoplastic particle transfer across the placenta involves energy-dependent uptake, material transfer, and particle e ux to the fetal side [20]. As it pertains to nanoplastic particle deposition within the tissues, it remains unclear if the nanopolystyrene particles have been taken up by the fetal cells, if they remain in the vasculature, migrate to the interstitial space, or if they are returned to the maternal circulation in bulk.…”

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

“…The placenta perfusion experiments were performed on a human ex vivo placenta perfusion model at the Swiss Federal Laboratories for Materials Science and Technology (Empa) as described previously. [37][38][39] Criteria for a successful perfusions were leak from fetal to maternal circulation of <4 ml h −1 and stable pH (7.2-7.4). The perfusion medium (PM) was M199 tissue culture medium (Sigma, St Louis, MO, USA) diluted 1 : 2 with Earl's buffer and supplemented with 1 g L −1 glucose (Sigma, St Louis, MO, USA), 10 g L −1 bovine serum albumin (AppliChem GmbH, Darmstadt, Germany), 10 g L −1 dextran 40 (Sigma, St Louis, MO, USA), 2500 IU L −1 sodium heparin (B. Braun Medical AG, Melsungen, Germany), 250 mg L −1 amoxicillin (GlaxoSmithKline AG, Brentford, UK) and 2.2 g L −1 sodium bicarbonate (Merck, Darmstadt, Germany).…”

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

“…4 included ex vivo perfusion studies emphasized the effect of surface modification (e.g. , PEGylation and carboxylation) on the transplacental passage of engineered NPs [ 31 , 37 , 41 , 42 ]. The overall consensus was that PEGylation increases the transplacental particle transport, while carboxylation (e.g.…”

“…Placental accumulation of all NPs regardless of modification and perfusion direction. [ 42 ] Human 32 PS NPs/ fluorophore, amine, or carboxyl 63 ± 10, 71 ± 11, 78 ± 20, 88 ± 7, 89 ± 3, 181 ± 11, 224 ± 17, 455 ± 32, 451 ± 28, 494 ± 29, or 499 ± 8 b 25 μg/mL c / 6 h Fluorescence microscopy / Plain and small carboxylated PS NPs but not aminylated PS NPs transferred across the placenta after 6 h of perfusion. [ 43 ] Human 16 PS NPs/ fluorophore 50, 80, 240, or 500 a 25 μg/mL c / 6 h / TEM PS NPs up to 240 nm crossed the placenta and reached the fetal circuit.…”