Nanoparticle transport across the placental barrier: pushing the field forward!

The human placenta is a multifunctional organ constituting the barrier between maternal and fetal tissues. Nanoparticles can cross the placental barrier, and there is increasing evidence that the extent of transfer is dependent on particle characteristics and functionalization. While translocated particles may pose risks to the growing fetus particles may also be engineered to enable new particle-based therapies in pregnancy. In both cases, a comprehensive understanding of nanoparticle uptake, accumulation and translocation is indispensable and requires predictive placental transfer models. We examine and evaluate the current literature to draw first conclusions on the possibility to steer translocation of nanoparticles. In addition, we discuss if current placental models are suitable for nanoparticle transfer studies and suggest strategies to improve their predictability.

[1]  Hak Soo Choi,et al.  Rapid translocation of nanoparticles from the lung airspaces to the body , 2010, Nature Biotechnology.

[2]  Hazem Ali,et al.  Preparation, characterization, and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model. , 2013, International journal of pharmaceutics.

[3]  M. Mahmoudi,et al.  Protein-nanoparticle interactions: opportunities and challenges. , 2011, Chemical reviews.

[4]  Peter Wick,et al.  Barrier Capacity of Human Placenta for Nanosized Materials , 2009, Environmental health perspectives.

[5]  H. Bouwmeester,et al.  Translocation of differently sized and charged polystyrene nanoparticles in in vitro intestinal cell models of increasing complexity , 2015, Nanotoxicology.

[6]  Fan Zhang,et al.  The genotype-dependent influence of functionalized multiwalled carbon nanotubes on fetal development. , 2014, Biomaterials.

[7]  M. Ferrari,et al.  Size of the nanovectors determines the transplacental passage in pregnancy: study in rats. , 2011, American journal of obstetrics and gynecology.

[8]  H. Krug,et al.  Bidirectional Transfer Study of Polystyrene Nanoparticles across the Placental Barrier in an ex Vivo Human Placental Perfusion Model , 2015, Environmental health perspectives.

[9]  Aldert H Piersma,et al.  A perspective on the developmental toxicity of inhaled nanoparticles. , 2015, Reproductive toxicology.

[10]  Hui Yang,et al.  Effects of gestational age and surface modification on materno-fetal transfer of nanoparticles in murine pregnancy , 2012, Scientific Reports.

[11]  T. Fennell,et al.  Distribution of carbon‐14 labeled C60 ([14C]C60) in the pregnant and in the lactating dam and the effect of C60 exposure on the biochemical profile of urine , 2010, Journal of applied toxicology : JAT.

[12]  Chen-Chun Chen,et al.  Nanoparticles can cross mouse placenta and induce trophoblast apoptosis. , 2013, Placenta.

[13]  P. Wick,et al.  Knocking at the door of the unborn child: engineered nanoparticles at the human placental barrier. , 2012, Swiss medical weekly.

[14]  Peter Wick,et al.  Transfer studies of polystyrene nanoparticles in the ex vivo human placenta perfusion model: key sources of artifacts , 2015, Science and technology of advanced materials.

[15]  K. Novoselov,et al.  Exploring the Interface of Graphene and Biology , 2014, Science.

[16]  Yaolin Xu,et al.  Surface charge and dosage dependent potential developmental toxicity and biodistribution of iron oxide nanoparticles in pregnant CD-1 mice. , 2014, Reproductive toxicology.

[17]  B. van Ravenzwaay,et al.  Assessment of an in vitro transport model using BeWo b30 cells to predict placental transfer of compounds , 2013, Archives of Toxicology.

[18]  S. Kežić,et al.  Progress and future of in vitro models to study translocation of nanoparticles , 2015, Archives of Toxicology.

[19]  Kenneth A Dawson,et al.  Nanoparticle accumulation and transcytosis in brain endothelial cell layers. , 2013, Nanoscale.

[20]  Jing Wang,et al.  Damaging Effects of Multi-walled Carbon Nanotubes on Pregnant Mice with Different Pregnancy Times , 2014, Scientific Reports.

[21]  E. Rytting Exploring the interactions of nanoparticles with multiple models of the maternal--fetal interface , 2015, Nanotoxicology.

[22]  R. Kannan,et al.  Transfer of PAMAM dendrimers across human placenta: prospects of its use as drug carrier during pregnancy. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[23]  B. Hong,et al.  Prospects and Challenges of Graphene in Biomedical Applications , 2013, Advanced materials.

[24]  Qiang Wu,et al.  Transfer of quantum dots from pregnant mice to pups across the placental barrier. , 2010, Small.

[25]  Xiangyu Bi,et al.  Nanoparticle size detection limits by single particle ICP-MS for 40 elements. , 2014, Environmental science & technology.

[26]  Wendelin J. Stark,et al.  Nanoparticles in biological systems. , 2011, Angewandte Chemie.

[27]  Kenneth A. Dawson,et al.  Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts , 2008, Proceedings of the National Academy of Sciences.

[28]  J. Zelikoff,et al.  Cadmium associated with inhaled cadmium oxide nanoparticles impacts fetal and neonatal development and growth. , 2012, Toxicological sciences : an official journal of the Society of Toxicology.

[29]  S. Hou,et al.  The Interplay of Size and Surface Functionality on the Cellular Uptake of Sub-10 nm Gold Nanoparticles. , 2015, ACS nano.

[30]  B. Fadeel Systems biology in nanosafety research. , 2015, Nanomedicine.

[31]  G. Hutchison,et al.  Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development , 2014, Molecular Psychiatry.

[32]  L. Knudsen,et al.  Quality assessment of a placental perfusion protocol. , 2010, Reproductive toxicology.

[33]  T. Kortulewski,et al.  Assessment of an in vitro model of pulmonary barrier to study the translocation of nanoparticles , 2014, Toxicology reports.

[34]  Marco P Monopoli,et al.  Biomolecular coronas provide the biological identity of nanosized materials. , 2012, Nature nanotechnology.

[35]  J. Keelan,et al.  Active transport across the human placenta: impact on drug efficacy and toxicity , 2006, Expert opinion on drug metabolism & toxicology.

[36]  M. Saunders,et al.  The toxicity, transport and uptake of nanoparticles in the in vitro BeWo b30 placental cell barrier model used within NanoTEST , 2015, Nanotoxicology.

[37]  T. Blankenship,et al.  Comparative placental structure. , 1999, Advanced drug delivery reviews.

[38]  Yasuo Yoshioka,et al.  Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. , 2011, Nature nanotechnology.

[39]  H. Takano,et al.  Demonstration of the Clathrin- and Caveolin-Mediated Endocytosis at the Maternal–Fetal Barrier in Mouse Placenta after Intravenous Administration of Gold Nanoparticles , 2013, The Journal of veterinary medical science.

[40]  A. Jaffa,et al.  In vitro simulation of placental transport: part I. Biological model of the placental barrier. , 2013, Placenta.

[41]  Bengt Fadeel,et al.  Interactions of engineered nanoparticles with organs protected by internal biological barriers. , 2013, Small.

[42]  R. Juliano The future of nanomedicine: Promises and limitations , 2012 .

[43]  Bengt Fadeel,et al.  Bridge over troubled waters: understanding the synthetic and biological identities of engineered nanomaterials. , 2013, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[44]  L. Knudsen,et al.  Modelling of human transplacental transport as performed in Copenhagen, Denmark. , 2014, Basic & clinical pharmacology & toxicology.

[45]  Pierangelo Metrangolo,et al.  Nanomedicine delivery: does protein corona route to the target or off road? , 2015, Nanomedicine.

[46]  Håkan Wallin,et al.  Correction: Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice , 2011, Particle and Fibre Toxicology.

[47]  Tracy K. Pettinger,et al.  Nanopharmaceuticals (part 1): products on the market , 2014, International journal of nanomedicine.

[48]  Ken Takeda,et al.  Nanoparticles Transferred from Pregnant Mice to Their Offspring Can Damage the Genital and Cranial Nerve Systems , 2009 .

[49]  L. Yates,et al.  Prescribing without evidence – pregnancy , 2012, British journal of clinical pharmacology.

[50]  S. Takeuchi,et al.  Fluid shear triggers microvilli formation via mechanosensitive activation of TRPV6 , 2015, Nature Communications.

[51]  H. M. Nielsen,et al.  In vitro placental model optimization for nanoparticle transport studies , 2012, International journal of nanomedicine.

[52]  N. Vargesson Thalidomide‐induced teratogenesis: History and mechanisms , 2015, Birth defects research. Part C, Embryo today : reviews.

[53]  Bengt Fadeel,et al.  Classification framework for graphene-based materials. , 2014, Angewandte Chemie.

[54]  G. Koren,et al.  The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs , 2011, Clinical pharmacology and therapeutics.

[55]  Martin Fussenegger,et al.  Microscale tissue engineering using gravity-enforced cell assembly. , 2004, Trends in biotechnology.

[56]  April Feswick,et al.  Distribution of silver nanoparticles in pregnant mice and developing embryos , 2012, Nanotoxicology.

[57]  Federica Valentini,et al.  Low doses of pristine and oxidized single-wall carbon nanotubes affect mammalian embryonic development. , 2011, ACS nano.

[58]  A. Jones,et al.  Nanoparticle geometry and surface orientation influence mode of cellular uptake. , 2013, ACS nano.

[59]  Håkan Wallin,et al.  Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice , 2010, Particle and Fibre Toxicology.

[60]  D. Huh,et al.  Placenta-on-a-chip: a novel platform to study the biology of the human placenta , 2016, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[61]  Takafumi Ninomiya,et al.  Gold nanoparticles as a vaccine platform: influence of size and shape on immunological responses in vitro and in vivo. , 2013, ACS nano.

[62]  Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia , 2014, Particle and Fibre Toxicology.

[63]  V. Weissig,et al.  Nanopharmaceuticals (part 2): products in the pipeline , 2015, International journal of nanomedicine.

[64]  P. Myllynen,et al.  Placental transfer and metabolism: an overview of the experimental models utilizing human placental tissue. , 2013, Toxicology in vitro : an international journal published in association with BIBRA.

[65]  S. Lecoeur,et al.  The Role of the Placenta in Fetal Exposure to Xenobiotics: Importance of Membrane Transporters and Human Models for Transfer Studies , 2010, Drug Metabolism and Disposition.

[66]  C. Sibley,et al.  Review: Transport across the placenta of mice and women. , 2013, Placenta.

[67]  Guibin Jiang,et al.  Effective Surface Charge Density Determines the Electrostatic Attraction between Nanoparticles and Cells , 2012 .

[68]  L. Knudsen,et al.  Kinetics of silica nanoparticles in the human placenta , 2015, Nanotoxicology.

[69]  M. Panigel,et al.  [Radioangiographic study of circulation in the villi and intervillous space of isolated human placental cotyledon kept viable by perfusion]. , 1967, Journal de physiologie.

[70]  V. Ganapathy,et al.  Placental transporters relevant to drug distribution across the maternal-fetal interface. , 2000, The Journal of pharmacology and experimental therapeutics.

[71]  Hans Bouwmeester,et al.  Translocation of positively and negatively charged polystyrene nanoparticles in an in vitro placental model. , 2015, Toxicology in vitro : an international journal published in association with BIBRA.

[72]  Navid B. Saleh,et al.  Investigating the effects of functionalized carbon nanotubes on reproduction and development in Drosophila melanogaster and CD-1 mice. , 2011, Reproductive toxicology.

[73]  Devon L. Greyson,et al.  Prescription drug use during pregnancy in developed countries: a systematic review , 2011, Pharmacoepidemiology and drug safety.

[74]  Manuela Semmler-Behnke,et al.  Supplementary information Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat , 2014 .

[75]  Peter Wick,et al.  Determination of the transport rate of xenobiotics and nanomaterials across the placenta using the ex vivo human placental perfusion model. , 2013, Journal of visualized experiments : JoVE.

[76]  P. Wick,et al.  Effect of particle agglomeration in nanotoxicology , 2015, Archives of Toxicology.

[77]  Peter Wick,et al.  Nanotoxicology: an interdisciplinary challenge. , 2011, Angewandte Chemie.

[78]  S. Vranic,et al.  Development of an in vitro model of human bronchial epithelial barrier to study nanoparticle translocation. , 2015, Toxicology in vitro : an international journal published in association with BIBRA.

[79]  P. Myllynen,et al.  Kinetics of gold nanoparticles in the human placenta. , 2008, Reproductive toxicology.

[80]  Antonio Pietroiusti,et al.  Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice , 2013, Particle and Fibre Toxicology.

[81]  Gottfried Dohr,et al.  Nanomaterial interference with early human placenta: Sophisticated matter meets sophisticated tissues. , 2013, Reproductive toxicology.

[82]  A. Malek,et al.  The impact of cocaine and heroin on the placental transfer of methadone , 2009, Reproductive biology and endocrinology : RB&E.

[83]  L. Knudsen,et al.  Modeling placental transport: correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion. , 2009, Toxicology in vitro : an international journal published in association with BIBRA.

[84]  Arezou A Ghazani,et al.  Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. , 2006, Nano letters.

[85]  Kirsi Vähäkangas,et al.  Ex vivo perfusion of the human placental cotyledon: implications for anesthetic pharmacology , 2000 .

[86]  F. Sonntag,et al.  A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. , 2015, Lab on a chip.

[87]  Diwei Ho,et al.  Therapeutic and safety considerations of nanoparticle-mediated drug delivery in pregnancy. , 2015, Nanomedicine.