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000885520 1001_ $$0P:(DE-HGF)0$$aSokolova, Viktoriya$$b0
000885520 245__ $$aUltrasmall gold nanoparticles (2 nm) can penetrate and enter cell nuclei in an in vitro 3D brain spheroid model
000885520 260__ $$a[Amsterdam]$$bElsevier$$c2020
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000885520 520__ $$aThe neurovascular unit (NVU) is a complex functional and anatomical structure composed of endothelial cells and their blood-brain barrier (BBB) forming tight junctions. It represents an efficient barrier for molecules and drugs. However, it also prevents a targeted transport for the treatment of cerebral diseases. The uptake of ultrasmall nanoparticles as potential drug delivery agents was studied in a three-dimensional co-culture cell model (3D spheroid) composed of primary human cells (astrocytes, pericytes, endothelial cells). Multicellular 3D spheroids show reproducible NVU features and functions. The spheroid core is composed mainly of astrocytes, covered with pericytes, while brain endothelial cells form the surface layer, establishing the NVU that regulates the transport of molecules. After 120 h cultivation, the cells self-assemble into a 350 µm spheroid as shown by confocal laser scanning microscopy. The passage of different types of fluorescent ultrasmall gold nanoparticles (core diameter 2 nm) both into the spheroid and into three constituting cell types was studied by confocal laser scanning microscopy. Three kinds of covalently fluorophore-conjugated gold nanoparticles were used: One with fluorescein (FAM), one with Cy3, and one with the peptide CGGpTPAAK-5,6-FAM-NH2. In 2D cell co-culture experiments, it was found that all three kinds of nanoparticles readily entered all three cell types. FAM- and Cy3-labelled nanoparticles were able to enter the cell nucleus as well. The three dissolved dyes alone were not taken up by any cell type. A similar situation evolved with 3D spheroids: The three kinds of nanoparticles entered the spheroid, but the dissolved dyes did not. The presence of a functional blood-brain barrier was demonstrated by adding histamine to the spheroids. In that case, the blood-brain barrier opened, and dissolved dyes like a FITC-labelled antibody and FITC alone entered the spheroid. In summary, our results qualify ultrasmall gold nanoparticles as suitable carriers for imaging or drug delivery into brain cells (sometimes including the nucleus), brain cell spheroids, and probably also into the brain.
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000885520 7001_ $$0P:(DE-HGF)0$$aNzou, Goodwell$$b1
000885520 7001_ $$0P:(DE-HGF)0$$avan der Meer, Selina B.$$b2
000885520 7001_ $$0P:(DE-HGF)0$$aRuks, Tatjana$$b3
000885520 7001_ $$0P:(DE-Juel1)130695$$aHeggen, Marc$$b4
000885520 7001_ $$0P:(DE-HGF)0$$aLoza, Kateryna$$b5
000885520 7001_ $$0P:(DE-HGF)0$$aHagemann, Nina$$b6
000885520 7001_ $$0P:(DE-HGF)0$$aMurke, Florian$$b7
000885520 7001_ $$0P:(DE-HGF)0$$aGiebel, Bernd$$b8
000885520 7001_ $$0P:(DE-HGF)0$$aHermann, Dirk M.$$b9
000885520 7001_ $$0P:(DE-HGF)0$$aAtala, Anthony J.$$b10
000885520 7001_ $$00000-0002-1641-7068$$aEpple, Matthias$$b11$$eCorresponding author
000885520 773__ $$0PERI:(DE-600)2173841-5$$a10.1016/j.actbio.2020.04.023$$gVol. 111, p. 349 - 362$$p349 - 362$$tActa biomaterialia$$v111$$x1742-7061$$y2020
000885520 8564_ $$uhttps://juser.fz-juelich.de/record/885520/files/Sokolova%20et%20al%202020.pdf$$yPublished on 2020-05-13. Available in OpenAccess from 2021-05-13.
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