4.6 Article

Uptake and Transport of Superparamagnetic Iron Oxide Nanoparticles through Human Brain Capillary Endothelial Cells

Journal

ACS CHEMICAL NEUROSCIENCE
Volume 4, Issue 10, Pages 1352-1360

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/cn400093z

Keywords

blood-brain barrier; magnetic nanoparticles; drug delivery; TEER; astrocytes; endothelial cells; in vitro

Funding

  1. Danish Medical Research Council [271-06-0211]
  2. Spar Nord Fund
  3. Obelske Family Fund, Fonden til laegevidenskabens fremme, v/A.P. Moller og Hustru Chastine Mc-Kinney Mollers Fond

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The blood-brain barrier (BBB) formed by brain capillary endothelial cells (BCECs) constitutes a firm physical, chemical, and immunological barrier, making the brain accessible to only a few percent of potential drugs intended for treatment inside the central nervous system. With the purpose of overcoming the restraints of the BBB by allowing the transport of drugs, siRNA, or DNA into the brain, a novel approach is to use superparamagnetic iron oxide nanoparticles (SPIONs) as drug carriers. The aim of this study was to investigate the ability of fluorescent SPIONs to pass through human brain microvascular endothelial cells facilitated by an external magnet. The ability of SPIONs to penetrate the barrier was shown to be significantly stronger in the presence of an external magnetic force in an in vitro BBB model. Hence, particles added to the luminal side of the in vitro BBB model were found in astrocytes cocultured at a remote distance on the abluminal side, indicating that particles were transported through the barrier and taken up by astrocytes. Addition of the SPIONs to the culture medium did not negatively affect the viability of the endothelial cells. The magnetic force-mediated dragging of SPIONs through BCECs may denote a novel mechanism for the delivery of drugs to the brain.

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