In vitro placental model optimization for nanoparticle transport studies

Laura Cartwright, Marie Sønnegaard Poulsen, Hanne Mørck Nielsen, Giulio Pojana, Lisbeth E. Knudsen, Margaret Saunders, Erik Rytting

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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 signifcant 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 fuorescein sodium transport. Following the determination of nontoxic concentrations of fuorescent 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, fuorescence readings, and confocal microscopy indicated both cellular uptake of the fuorescent 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.

Original languageEnglish (US)
Pages (from-to)497-510
Number of pages14
JournalInternational Journal of Nanomedicine
Volume7
StatePublished - 2012

Fingerprint

Nanoparticles
Polystyrenes
polycarbonate
Pore size
Hope
Cells
Transcytosis
Choriocarcinoma
Nanotechnology
Acoustic impedance
Confocal microscopy
Tight Junctions
Trophoblasts
Polycarbonates
In Vitro Techniques
Transmission Electron Microscopy
Electric Impedance
Biocompatibility
Particle Size
Confocal Microscopy

Keywords

  • BeWo cells
  • Model optimization
  • Nanoparticles
  • Nanotoxicology
  • Placenta
  • Transport

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Organic Chemistry
  • Drug Discovery

Cite this

Cartwright, L., Poulsen, M. S., Nielsen, H. M., Pojana, G., Knudsen, L. E., Saunders, M., & Rytting, E. (2012). In vitro placental model optimization for nanoparticle transport studies. International Journal of Nanomedicine, 7, 497-510.

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, Vol. 7, 2012, p. 497-510.

Research output: Contribution to journalArticle

Cartwright, L, Poulsen, MS, Nielsen, HM, Pojana, G, Knudsen, LE, Saunders, M & Rytting, E 2012, 'In vitro placental model optimization for nanoparticle transport studies', International Journal of Nanomedicine, vol. 7, pp. 497-510.
Cartwright L, Poulsen MS, Nielsen HM, Pojana G, Knudsen LE, Saunders M et al. In vitro placental model optimization for nanoparticle transport studies. International Journal of Nanomedicine. 2012;7:497-510.
Cartwright, Laura ; Poulsen, Marie Sønnegaard ; Nielsen, Hanne Mørck ; Pojana, Giulio ; Knudsen, Lisbeth E. ; Saunders, Margaret ; Rytting, Erik. / In vitro placental model optimization for nanoparticle transport studies. In: International Journal of Nanomedicine. 2012 ; Vol. 7. pp. 497-510.
@article{b8f205b5ca3a4e008d80265c6ab32eb6,
title = "In vitro placental model optimization for nanoparticle transport studies",
abstract = "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 signifcant 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{\circledR} insert type and pore size, the investigation of barrier properties by transmission electron microscopy, tight junction staining, transepithelial electrical resistance, and fuorescein sodium transport. Following the determination of nontoxic concentrations of fuorescent 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, fuorescence readings, and confocal microscopy indicated both cellular uptake of the fuorescent 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.",
keywords = "BeWo cells, Model optimization, Nanoparticles, Nanotoxicology, Placenta, Transport",
author = "Laura Cartwright and Poulsen, {Marie S{\o}nnegaard} and Nielsen, {Hanne M{\o}rck} and Giulio Pojana and Knudsen, {Lisbeth E.} and Margaret Saunders and Erik Rytting",
year = "2012",
language = "English (US)",
volume = "7",
pages = "497--510",
journal = "International Journal of Nanomedicine",
issn = "1176-9114",
publisher = "Dove Medical Press Ltd.",

}

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 signifcant 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 fuorescein sodium transport. Following the determination of nontoxic concentrations of fuorescent 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, fuorescence readings, and confocal microscopy indicated both cellular uptake of the fuorescent 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 signifcant 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 fuorescein sodium transport. Following the determination of nontoxic concentrations of fuorescent 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, fuorescence readings, and confocal microscopy indicated both cellular uptake of the fuorescent 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 - BeWo cells

KW - Model optimization

KW - Nanoparticles

KW - Nanotoxicology

KW - Placenta

KW - Transport

UR - http://www.scopus.com/inward/record.url?scp=84856658620&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856658620&partnerID=8YFLogxK

M3 - Article

VL - 7

SP - 497

EP - 510

JO - International Journal of Nanomedicine

JF - International Journal of Nanomedicine

SN - 1176-9114

ER -