Interaction of functionalized superparamagnetic iron oxide nanoparticles with brain structures.

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State: Public
Version: Final published version
License: All rights reserved
Serval ID
serval:BIB_42D3E5677053
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Interaction of functionalized superparamagnetic iron oxide nanoparticles with brain structures.
Journal
Journal of Pharmacology and Experimental Therapeutics
Author(s)
Cengelli F., Maysinger D., Tschudi-Monnet F., Montet X., Corot C., Petri-Fink A., Hofmann H., Juillerat-Jeanneret L.
ISSN
0022-3565
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
318
Number
1
Pages
108-116
Language
english
Abstract
Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) combined with magnetic resonance imaging (MRI) are under clinical evaluation to enhance detection of neurodegenerative diseases. A major improvement would be to link therapeutic drugs to the SPIONs to achieve targeted drug delivery, either at the cell surface or intracellularly, together with active disease detection, without inducing cell reaction. Our objectives were to define the characteristics of SPIONS able to achieve cell-specific interaction with brain-derived structures. Our system consisted in an iron oxide core (9-10 nm diameter) coated either with dextran (Sinerem and Endorem) or various functionalized polyvinyl alcohols (PVAs) (PVA-SPIONs). We investigated the cellular uptake, cytotoxicity, and interaction of these various nanoparticles with brain-derived endothelial cells, microglial cells, and differentiating three-dimensional aggregates. None of the nanoparticles coated with dextran or the various PVAs was cytotoxic or induced the production of the inflammatory mediator NO used as a reporter for cell activation. AminoPVA-SPIONs were taken up by isolated brain-derived endothelial and microglial cells at a much higher level than the other SPIONs, and no inflammatory activation of these cells was observed. AminoPVA-SPIONs did not invade brain cells aggregates lower than the first cell layer and did not induce inflammatory reaction in the aggregates. Fluorescent aminoPVA-SPIONs derivatized with a fluorescent reporter molecule and confocal microscopy demonstrated intracellular uptake by microglial cells. Fluorescent aminoPVA-SPIONs were well tolerated by mice. Therefore, functionalized aminoPVA-SPIONs represent biocompatible potential vector systems for drug delivery to the brain that may be combined with MRI detection of active lesions in neurodegenerative diseases.
Keywords
Animals, Brain, Cells, Cultured, Ferric Compounds, Magnetic Resonance Imaging, Mice, Mice, Inbred C57BL, Nanostructures, Rats
Pubmed
Web of science
Create date
29/01/2008 19:33
Last modification date
14/07/2020 6:21
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