Impact of particle size and surface modification on gold nanoparticle penetration into human placental microtissues.

AIM Nanoparticle-based drug carriers hold great promise for the development of targeted therapies in pregnancy with reduced off-target effects. Here, we performed a mechanistic in vitro study on placental localization and penetration of gold nanoparticles (AuNPs) in dependence of particle size and surface modification. MATERIALS & METHODS AuNP uptake and penetration in human placental coculture microtissues was assessed by inductively coupled plasma-mass spectrometry, transmission electron microscopy and laser ablation-inductively coupled plasma-mass spectrometry. RESULTS Higher uptake and deeper penetration was observed for smaller (3-4 nm) or sodium carboxylate-modified AuNPs than for larger (13-14 nm) or PEGylate AuNPs, which barely passed the trophoblast barrier layer. CONCLUSION It is possible to steer placental uptake and penetration of AuNPs by tailoring their properties, which is a prerequisite for the development of targeted therapies in pregnancy.

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

[2]  Thorsten Fleiter,et al.  Syntheses and characterization of lisinopril-coated gold nanoparticles as highly stable targeted CT contrast agents in cardiovascular diseases. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[3]  S. Kannan,et al.  Transport and biodistribution of dendrimers across human fetal membranes: implications for intravaginal administration of dendrimer-drug conjugates. , 2010, Biomaterials.

[4]  Yuliang Zhao,et al.  Quantitative analysis of gold nanoparticles in single cells by laser ablation inductively coupled plasma-mass spectrometry. , 2014, Analytical chemistry.

[5]  V. Dressler,et al.  Review of the applications of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to the analysis of biological samples , 2014 .

[6]  D. Evain-Brion,et al.  A comparison of placental development and endocrine functions between the human and mouse model. , 2003, Human reproduction update.

[7]  Vincent M Rotello,et al.  Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. , 2004, Bioconjugate chemistry.

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

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

[10]  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.

[11]  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.

[12]  M. Swihart,et al.  Gold nanoparticles surface-terminated with bifunctional ligands , 2004 .

[13]  C. Roberts,et al.  Growth and function of the normal human placenta. , 2004, Thrombosis research.

[14]  M. Zheng,et al.  Ethylene glycol monolayer protected nanoparticles: synthesis, characterization, and interactions with biological molecules. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[15]  Peter Wick,et al.  Nanoparticle transport across the placental barrier: pushing the field forward! , 2016, Nanomedicine.

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

[17]  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.

[18]  V. Rotello,et al.  Nanoparticle-templated assembly of viral protein cages. , 2006, Nano letters.

[19]  David J Brayden,et al.  Progress in the delivery of nanoparticle constructs: towards clinical translation. , 2014, Current opinion in pharmacology.

[20]  Norbert Jakubowski,et al.  Quantitative imaging of gold and silver nanoparticles in single eukaryotic cells by laser ablation ICP-MS. , 2012, Analytical chemistry.

[21]  E. Rytting,et al.  Fetal drug therapy , 2022, Clinical Pharmacology During Pregnancy.

[22]  D. Needham,et al.  Range and magnitude of the steric pressure between bilayers containing phospholipids with covalently attached poly(ethylene glycol). , 1995, Biophysical journal.

[23]  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.

[24]  U. Karst,et al.  Study on aerosol characteristics and fractionation effects of organic standard materials for bioimaging by means of LA-ICP-MS , 2015 .

[25]  E. Reynolds THE USE OF LEAD CITRATE AT HIGH pH AS AN ELECTRON-OPAQUE STAIN IN ELECTRON MICROSCOPY , 1963, The Journal of cell biology.

[26]  A. Matusch,et al.  Bioimaging mass spectrometry of trace elements - recent advance and applications of LA-ICP-MS: A review. , 2014, Analytica chimica acta.

[27]  T. Cindrova-Davies The therapeutic potential of antioxidants, ER chaperones, NO and H2S donors, and statins for treatment of preeclampsia , 2014, Front. Pharmacol..

[28]  Giulio Caracciolo,et al.  Effect of polyethyleneglycol (PEG) chain length on the bio-nano-interactions between PEGylated lipid nanoparticles and biological fluids: from nanostructure to uptake in cancer cells. , 2014, Nanoscale.

[29]  Arthur G Erdman,et al.  The big picture on nanomedicine: the state of investigational and approved nanomedicine products. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[30]  S. Vollset,et al.  Exposure to antiepileptic drugs in utero and child development: A prospective population‐based study , 2013, Epilepsia.

[31]  P. Skehan,et al.  Morphological differentiation of human choriocarcinoma cells induced by methotrexate. , 1979, Cancer research.

[32]  U. Karst,et al.  Elemental bioimaging of haematoxylin and eosin-stained tissues by laser ablation ICP-MS , 2013 .

[33]  N. Denora,et al.  Oxcarbazepine-loaded polymeric nanoparticles: development and permeability studies across in vitro models of the blood–brain barrier and human placental trophoblast , 2015, International journal of nanomedicine.

[34]  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.

[35]  E. Rytting,et al.  Transport of digoxin-loaded polymeric nanoparticles across BeWo cells, an in vitro model of human placental trophoblast. , 2015, Therapeutic delivery.

[36]  Y. Barenholz,et al.  Annals of the New York Academy of Sciences Nanomedicines: Addressing the Scientific and Regulatory Gap , 2022 .

[37]  Norbert Jakubowski,et al.  Relating surface-enhanced Raman scattering signals of cells to gold nanoparticle aggregation as determined by LA-ICP-MS micromapping , 2014, Analytical and Bioanalytical Chemistry.

[38]  Parag Aggarwal,et al.  Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. , 2008, Molecular pharmaceutics.

[39]  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.

[40]  D. Hare,et al.  Quantification strategies for elemental imaging of biological samples using laser ablation-inductively coupled plasma-mass spectrometry. , 2012, The Analyst.

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

[42]  Peter Wick,et al.  A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment. , 2016, Nanoscale.

[43]  T. Tomson,et al.  Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry , 2011, The Lancet Neurology.

[44]  B. Burmahl The big picture. , 2000, Health facilities management.

[45]  T. Reemtsma,et al.  Quantification of Al2O3 nanoparticles in human cell lines applying inductively coupled plasma mass spectrometry (neb-ICP-MS, LA-ICP-MS) and flow cytometry-based methods , 2014, Journal of Nanoparticle Research.

[46]  T. Johns,et al.  Targeted nanoparticle delivery of doxorubicin into placental tissues to treat ectopic pregnancies. , 2013, Endocrinology.

[47]  P. Stahl,et al.  Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes , 1983, The Journal of cell biology.

[48]  Wojciech G. Lesniak,et al.  Fetal uptake of intra-amniotically delivered dendrimers in a mouse model of intrauterine inflammation and preterm birth. , 2014, Nanomedicine : nanotechnology, biology, and medicine.

[49]  K. Widdows,et al.  Tumor-homing peptides as tools for targeted delivery of payloads to the placenta , 2016, Science Advances.

[50]  Raimo Hartmann,et al.  Surface Functionalization of Nanoparticles with Polyethylene Glycol: Effects on Protein Adsorption and Cellular Uptake. , 2015, ACS nano.

[51]  Elodie Boisselier,et al.  Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. , 2009, Chemical Society reviews.

[52]  Erik C. Dreaden,et al.  The Golden Age: Gold Nanoparticles for Biomedicine , 2012 .

[53]  P. G. de Gennes,et al.  Polymers at an interface; a simplified view , 1987 .