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Table 1 Basic characteristics of the 15 in vitro studies investigating the maternal-fetal transfer of engineered NPs

From: 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

Ref Cell type Exposure Detection technique Main findings
Particle type/coating or label Size (nm) Dose/incubation period (Semi-) Quantitative Qualitative
Placental trophoblast monolayer
 [22] BeWo b30a Ag and Ag2S NPs/lipoic acid, citrate, or PEI 28 ± 2, 47 ± 5, 48 ± 5, or 51 ± 5c 1 μg/mL/ 4, 6, 18, and 24 h ICP-MS and spICP-MS / Internalization and transfer of different Ag NP types in the BeWo b30 cell layer dependent on surface chemistry.
 [23] BeWo b30 Au NPs/ PEG 10b 3.6 × 1010 particles/mL/6, 24, and 48 h / AMG and TEM After exposure for 6 h, 24 h, and 48 h, aggregates of Au NPs detected in BeWo b30 cells.
 [24] BeWo b30a Fe3O4 NPs/Na-oleate 8b 50 or 100 μg/mLe/ 24 h / Bright-field light microscopy and TEM Increased transport of Fe3O4 across and uptake in BeWo b30 cells NPs after Na-oleate-coating.
 [24] BeWo b30a SiO2 NPs/fluorophore 25 or 50b 25 or 50 μg/mLe/ 6 h Fluorescence microscopy Confocal microscopy SiO2 NPs crossed the BeWo b30 cells without a significant effect of particle size or concentration on transport or internalization.
 [25] BeWo b30a SiO2 NPs/fluorophore 25 or 50b 100 μg/mLe/ 24 hf Fluorescence microscopy Confocal microscopy Limited transport of SiO2 NPs across the BeWo b30 cells. Confocal microscopy visually confirmed particle accumulation in the cells.
 [26] BeWo b30a PS NPs/fluorophore 50 or 100b 500 μg/mL/ 24 hf Fluorescence microscopy Confocal microscopy Suggested size-dependent transport and cellular uptake as 50 nm PS NPs transferred to the fetal compartment at a higher rate compared to 100 nm PS NPs.
 [27] 3A-sub-E PS NPs/carboxyl and fluorophore 20, 40, 100, 200, or 500b 10 μg/mL/ 4 h Flow cytometry and confocal microscopy TEM Differentially sized fluorescent PS NPs present in the trophoblast cells after 4 h of exposure, Cellular NP uptake highest and lowest for 40 nm and 500 nm PS NPs, respectively.
 [28] BeWo b30a PS NPs/carboxyl and fluorophore 50b 10 μg/mL/ 24 h Fluorescence microscopy / Limited translocation of PS NPs across the BeWo b30 cell layer without relation to NP charge.
 [29] HTR-8 PM2.5 <2500d 0.5 μg/mL/ 24 and 48 h / TEM PM2.5 particle uptake visualized within the inner mitochondrial membranes of exposed first trimester placental cells without difference in the 24 h and 48 h exposure groups.
 [30] HTR-8 Wood smoke particles < 1000d 0.5 μg/mL/ 48 h / TEM Wood smoke particles entered the cell and localized to the mitochondria in trophoblast cells, causing structural damage.
Co-culture
 [31] BeWo b30/ HPEC-A2a Au NPs/carboxyl or PEG 3.5 ± 1.2 or 4.5 ± 1.5c 25 or 50 μg/mL/ 24 h ICP-MS LA-ICP-MS and TEM PEGylated and carboxylated Au NPs crossed the co-culture in low amounts. Higher cellular uptake for carboxylated Au NPs, and slightly increased translocation for PEGylated Au NPs.
 [32] BeWo b30/ HVMF Au NPs/carboxyl or PEG 3.5 ± 1.2, 4.5 ± 1.5, 13.5 ± 3, or 14.0 ± 3.5c 50 μg/mL/ 24 h ICP-MS LA-ICP-MS and TEM Higher uptake for the smaller, carboxylated Au NPs compared to the larger, PEGylated Au NPs, which barely passed the co-culture.
 [33] BeWo/hPC-PLa SPIONs/starch, PEI, or CMX n.d. 200 μg/mL/ 3 or 24 h AAS and MPS Bright-field light microscopy and confocal microscopy PEI-coated SPIONs (cationic) remained primarily in the co-culture. Starch- and CMX-coated SPIONS (neutral and anionic, respectively) were able to pass the cell layer to a greater extent.
 [34] BeWo b30/ HPEC-A2a TiO2 NPs/ amine or carboxyl 4 to 8b 1 μg/mL/ 6 or 24 h SF-ICP-MS / No transplacental transfer of TiO2 NPs. Both types internalized in the BeWo b30 and HPEC-A2 cells of the co-culture.
 [35] BeWo b30/ HPEC-A2a PS NPs/ fluorophore 49 or 70b 50 or 500 μg/mL/ 24 hf Fluorescence microscopy / 70 nm PS NPs did not cross the co-culture. Small amounts of 49 nm PS NPs detected in the basolateral compartment after 24 h of exposure. Similar results for static and shaken conditions.
 [36] BeWo b30/ HPEC-A2a PS NPs/ fluorophore and carboxyl 46.3 ± 6.0c 10 or 100 μg/mL/ 24 h AF4-UV Confocal microscopy Within 24 h, no transport across the co-culture for both concentrations of PS NPs. Internalization of PS NPs in BeWo cells shown by confocal microscopy.
  1. Data are shown as mean ± standard deviation, acells grown on Transwell inserts, bprimary particle size stated by the manufacturer, cprimary particle size determined by TEM, dfilter pore size, e0.5 mL apically applied, 1.5 mL basolaterally applied, fincubation under shaken conditions
  2. Abbreviations - 3A-sub-E human SV40-transformed 3A-Sub-E trophoblast cell line, AAS atomic absorption spectrometry, AF4 asymmetrical flow field-flow fractionation system, AFM atomic force microscopy, Au gold, BeWo b30 human placental choriocarcinoma cell line, CMX carboxymethyl dextran, Fe3O4 magnetite or iron oxide, hPC-PL primary human placental pericytes, HPEC-A2 human SV40-transformed microvascular placental venous endothelial cells, HVMF human villous mesenchymal fibroblasts, ICP-MS inductively coupled plasma-mass spectrometry, LA-ICP-MS laser ablation-inductively coupled plasma-mass spectrometry, MPS magnetic particle spectroscopy, Na sodium, NP nanoparticle, PEI poly(ethyleneimine), PEG poly(ethylene glycol), PM2.5 particulate matter smaller than 2.5 μm in diameter, PS polystyrene, SiO2 silicon dioxide or silica, SPIONs superparamagnetic iron oxide nanoparticles, TEM transmission electron microscopy, TiO2 titanium dioxide