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@ARTICLE{Sokolova:885520,
      author       = {Sokolova, Viktoriya and Nzou, Goodwell and van der Meer,
                      Selina B. and Ruks, Tatjana and Heggen, Marc and Loza,
                      Kateryna and Hagemann, Nina and Murke, Florian and Giebel,
                      Bernd and Hermann, Dirk M. and Atala, Anthony J. and Epple,
                      Matthias},
      title        = {{U}ltrasmall gold nanoparticles (2 nm) can penetrate and
                      enter cell nuclei in an in vitro 3{D} brain spheroid model},
      journal      = {Acta biomaterialia},
      volume       = {111},
      issn         = {1742-7061},
      address      = {[Amsterdam]},
      publisher    = {Elsevier},
      reportid     = {FZJ-2020-03900},
      pages        = {349 - 362},
      year         = {2020},
      abstract     = {The 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.},
      cin          = {ER-C-1},
      ddc          = {530},
      cid          = {I:(DE-Juel1)ER-C-1-20170209},
      pnm          = {143 - Controlling Configuration-Based Phenomena (POF3-143)
                      / DFG project 286659497 - Bimetallische Nanopartikel der
                      Platinmetalle (Ru, Rh, Pd, Os, Ir, Pt) und des Silbers:
                      Synthese, Mikrostruktur und biologische Wirkung (286659497)},
      pid          = {G:(DE-HGF)POF3-143 / G:(GEPRIS)286659497},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32413579},
      UT           = {WOS:000543452700028},
      doi          = {10.1016/j.actbio.2020.04.023},
      url          = {https://juser.fz-juelich.de/record/885520},
}