Transport of ultrasmall gold nanoparticles (2 nm) across the blood–brain barrier in a six-cell brain spheroid model View Full Text


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Article Info

DATE

2020-10-22

AUTHORS

Viktoriya Sokolova, Gehad Mekky, Selina Beatrice van der Meer, Michael C. Seeds, Anthony J. Atala, Matthias Epple

ABSTRACT

The blood–brain barrier (BBB) is an efficient barrier for molecules and drugs. Multicellular 3D spheroids display reproducible BBB features and functions. The spheroids used here were composed of six brain cell types: Astrocytes, pericytes, endothelial cells, microglia cells, oligodendrocytes, and neurons. They form an in vitro BBB that regulates the transport of compounds into the spheroid. The penetration of fluorescent ultrasmall gold nanoparticles (core diameter 2 nm; hydrodynamic diameter 3–4 nm) across the BBB was studied as a function of time by confocal laser scanning microscopy, with the dissolved fluorescent dye (FAM-alkyne) as a control. The nanoparticles readily entered the interior of the spheroid, whereas the dissolved dye alone did not penetrate the BBB. We present a model that is based on a time-dependent opening of the BBB for nanoparticles, followed by a rapid diffusion into the center of the spheroid. After the spheroids underwent hypoxia (0.1% O2; 24 h), the BBB was more permeable, permitting the uptake of more nanoparticles and also of dissolved dye molecules. Together with our previous observations that such nanoparticles can easily enter cells and even the cell nucleus, these data provide evidence that ultrasmall nanoparticle can cross the blood brain barrier. More... »

PAGES

18033

References to SciGraph publications

  • 2020-06-17. Multicellular 3D Neurovascular Unit Model for Assessing Hypoxia and Neuroinflammation Induced Blood-Brain Barrier Dysfunction in SCIENTIFIC REPORTS
  • 2013-03-20. Multicellular Self-Assembled Spheroidal Model of the Blood Brain Barrier in SCIENTIFIC REPORTS
  • 2015-10-27. Three-Dimensional Blood-Brain Barrier Model for in vitro Studies of Neurovascular Pathology in SCIENTIFIC REPORTS
  • 2017-06-06. Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents in NATURE COMMUNICATIONS
  • 2013-08-28. Cerebral organoids model human brain development and microcephaly in NATURE
  • 2019-06-03. Suitability of 3D human brain spheroid models to distinguish toxic effects of gold and poly-lactic acid nanoparticles to assess biocompatibility for brain drug delivery in PARTICLE AND FIBRE TOXICOLOGY
  • 2015-09-21. Toxicology of nanosized titanium dioxide: an update in ARCHIVES OF TOXICOLOGY
  • 2018-10-31. Blood–brain-barrier organoids for investigating the permeability of CNS therapeutics in NATURE PROTOCOLS
  • 2017-07-12. Toxic effects and biodistribution of ultrasmall gold nanoparticles in ARCHIVES OF TOXICOLOGY
  • 2018-05-09. Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling in SCIENTIFIC REPORTS
  • 2009-06-12. Characteristics of compounds that cross the blood-brain barrier in BMC NEUROLOGY
  • 2015-10-21. Spontaneous penetration of gold nanoparticles through the blood brain barrier (BBB) in JOURNAL OF NANOBIOTECHNOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-020-75125-2

    DOI

    http://dx.doi.org/10.1038/s41598-020-75125-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1131953878

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33093563


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