In vitro placental model optimization for nanoparticle transport studies
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In vitro placental model optimization for nanoparticle transport studies. / Cartwright, Laura; Poulsen, Marie Sønnegaard; Nielsen, Hanne Mørck; Pojana, Giulio; Knudsen, Lisbeth E.; Saunders, Margaret; Rytting, Erik.
In: International Journal of Nanomedicine (Print), Vol. 7, 2012, p. 497-510.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - In vitro placental model optimization for nanoparticle transport studies
AU - Cartwright, Laura
AU - Poulsen, Marie Sønnegaard
AU - Nielsen, Hanne Mørck
AU - Pojana, Giulio
AU - Knudsen, Lisbeth E.
AU - Saunders, Margaret
AU - Rytting, Erik
PY - 2012
Y1 - 2012
N2 - BACKGROUND: Advances in biomedical nanotechnology raise hopes in patient populations but may also raise questions regarding biodistribution and biocompatibility, especially during pregnancy. Special consideration must be given to the placenta as a biological barrier because a pregnant woman's exposure to nanoparticles could have significant effects on the fetus developing in the womb. Therefore, the purpose of this study is to optimize an in vitro model for characterizing the transport of nanoparticles across human placental trophoblast cells.METHODS: The growth of BeWo (clone b30) human placental choriocarcinoma cells for nanoparticle transport studies was characterized in terms of optimized Transwell(®) insert type and pore size, the investigation of barrier properties by transmission electron microscopy, tight junction staining, transepithelial electrical resistance, and fluorescein sodium transport. Following the determination of nontoxic concentrations of fluorescent polystyrene nanoparticles, the cellular uptake and transport of 50 nm and 100 nm diameter particles was measured using the in vitro BeWo cell model.RESULTS: Particle size measurements, fluorescence readings, and confocal microscopy indicated both cellular uptake of the fluorescent polystyrene nanoparticles and the transcellular transport of these particles from the apical (maternal) to the basolateral (fetal) compartment. Over the course of 24 hours, the apparent permeability across BeWo cells grown on polycarbonate membranes (3.0 μm pore size) was four times higher for the 50 nm particles compared with the 100 nm particles.CONCLUSION: The BeWo cell line has been optimized and shown to be a valid in vitro model for studying the transplacental transport of nanoparticles. Fluorescent polystyrene nanoparticle transport was size-dependent, as smaller particles reached the basal (fetal) compartment at a higher rate.
AB - BACKGROUND: Advances in biomedical nanotechnology raise hopes in patient populations but may also raise questions regarding biodistribution and biocompatibility, especially during pregnancy. Special consideration must be given to the placenta as a biological barrier because a pregnant woman's exposure to nanoparticles could have significant effects on the fetus developing in the womb. Therefore, the purpose of this study is to optimize an in vitro model for characterizing the transport of nanoparticles across human placental trophoblast cells.METHODS: The growth of BeWo (clone b30) human placental choriocarcinoma cells for nanoparticle transport studies was characterized in terms of optimized Transwell(®) insert type and pore size, the investigation of barrier properties by transmission electron microscopy, tight junction staining, transepithelial electrical resistance, and fluorescein sodium transport. Following the determination of nontoxic concentrations of fluorescent polystyrene nanoparticles, the cellular uptake and transport of 50 nm and 100 nm diameter particles was measured using the in vitro BeWo cell model.RESULTS: Particle size measurements, fluorescence readings, and confocal microscopy indicated both cellular uptake of the fluorescent polystyrene nanoparticles and the transcellular transport of these particles from the apical (maternal) to the basolateral (fetal) compartment. Over the course of 24 hours, the apparent permeability across BeWo cells grown on polycarbonate membranes (3.0 μm pore size) was four times higher for the 50 nm particles compared with the 100 nm particles.CONCLUSION: The BeWo cell line has been optimized and shown to be a valid in vitro model for studying the transplacental transport of nanoparticles. Fluorescent polystyrene nanoparticle transport was size-dependent, as smaller particles reached the basal (fetal) compartment at a higher rate.
KW - Cell Line, Tumor
KW - Cell Survival
KW - Choriocarcinoma
KW - Female
KW - Fluorescent Dyes
KW - Humans
KW - Membrane Proteins
KW - Nanoparticles
KW - Particle Size
KW - Permeability
KW - Phosphoproteins
KW - Placenta
KW - Polycarboxylate Cement
KW - Polyesters
KW - Porosity
KW - Pregnancy
KW - Reproducibility of Results
KW - Transcytosis
KW - Uterine Neoplasms
KW - Zonula Occludens-1 Protein
U2 - 10.2147/IJN.S26601
DO - 10.2147/IJN.S26601
M3 - Journal article
C2 - 22334780
VL - 7
SP - 497
EP - 510
JO - International Journal of Nanomedicine (Print)
JF - International Journal of Nanomedicine (Print)
SN - 1176-9114
ER -
ID: 137757853