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Table 2 Basic characteristics of the 11 ex vivo placental perfusion 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 Species Sample size Exposure Detection technique Main findings
Particle type/coating or label Size (nm) Dose/ perfusion duration (Semi-) Quantitative Qualitative
 [37] Human 6 Ag NPs/ carboxyl or PEG 2–15 or 5–15b 40 or 75 μg/mLc/ 6 h spICP-MS Bright-field light microscopy Higher transplacental transport for smaller and PEGylated Ag NPs, while carboxylated Ag NPs accumulated more in placental tissue.
 [31] Human 6 Au NPs/ carboxyl or PEG 3.5 ± 1.2 or 4.5 ± 1.5b 25 μg/mLc/ 6 h LA- and SF-ICP-MS / Only PEGylated Au NPs observed in the fetal circulation. Placental tissue accumulation similar for both Au NP types.
 [38] Rat 11 Au NPs 20a 5.8 μg/mLd/ 3 h ICP-MS Hyper-spectral microscopy imaging Au NPs translocated across the rat placenta within 20 min of maternal infusion.
 [23] Human n.d. Au NPs/ PEG 15 or 30a 1.6 × 1011 or 1.6 × 1010 particles/mLd/ 18 min ICP-MS TEM and bright-field light microscopy No placental transfer of Au NPs detected. Visual confirmation of localization of NPs in syncytiotrophoblasts.
 [23] Human n.d. Au NPs/ PEG 10 or 15a 9.1 × 109 or 2.0 × 109 particles/mLc/ 6 h ICP-MS TEM and bright-field light microscopy No transfer of Au NPs across placenta regardless of NP size. Visual confirmation of placental tissue uptake of Au NPs.
 [25] Human 6 SiO2 NPs/ fluorophore 25 or 50a 100 μg/mLc/ 6 h Fluorescence microscopy Confocal microscopy Limited transfer of both SiO2 NP sizes to fetal perfusate despite placental accumulation.
 [39] Human n.d. Magnetic NPs/ starch or PEI 100 or 150a 50 μg/mLc/ 6 h Magnetic system Bright-field light microscopy Limited transfer of magnetic NPs from the maternal to the fetal circuit. Histological findings confirmed the presence of NPs in placental tissue.
 [34] Human 6 TiO2 NPs/ amine or carboxyl 4 to 8a 10 μg/mLc/ 6 h SF-ICP-MS / No translocation of both TiO2 NP types to the fetal circulation but accumulation in placental tissue.
 [40] Human 7 PS NPs/ fluorophore 80 or 500a 25 μg/mLc/ 6 h Fluorescence microscopy / 80 nm PS NPs able to cross the placenta, while 500 nm PS NPs retained in the placenta or maternal circuit.
 [41] Human 12 PS NPs/ fluorophore and carboxyl 43.7 ± 8, 44.1 ± 7.1, 220.5 ± 5.1, or 289.4 ± 10.2b 25 μg/mLe/ 6 h Fluorescence microscopy TEM Increased translocation of plain compared to carboxylated PS NPs after 6 h of perfusion. Significantly higher transfer of NPs in the fetal to maternal direction observed with bidirectional transfer studies. 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 ± 8b 25 μg/mLc/ 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 500a 25 μg/mLc/ 6 h / TEM PS NPs up to 240 nm crossed the placenta and reached the fetal circuit. 500 nm PS NPs mainly retained in the placental tissue and maternal circuit.
  1. Data are shown as mean ± standard deviation, aprimary particle size stated by the manufacturer, bprimary particle size determined by TEM, cre-circulating (closed) dual perfusion system, dopen dual perfusion system, ebidirectional perfusion
  2. Abbreviations - Ag silver, Ag2S silver sulfide, Au gold, ICP-MS inductively coupled plasma-mass spectrometry, LA-ICP-MS laser ablation-inductively coupled plasma-mass spectrometry, n.d. not defined, NP nanoparticle, PEI poly(ethyleneimine), PEG poly(ethylene glycol), PS polystyrene, SF-ICP-MS sector field-inductively coupled plasma-mass spectrometry, SiO2 silicon dioxide or silica, spICP-MS inductively coupled plasma-mass spectrometry in single-particle mode, TEM transmission electron microscopy, TiO2 titanium dioxide