The Application of Ultrasmall Gold Nanoparticles (2 nm) Functionalized with Doxorubicin in Three-Dimensional Normal and Glioblastoma Organoid Models of the Blood–Brain Barrier
Kathrin Kostka,
Viktoriya Sokolova,
Aya El-Taibany,
Benedikt Kruse,
Daniel Porada,
Natalie Wolff,
Oleg Prymak,
Michael C. Seeds,
Matthias Epple,
Anthony J. Atala
Affiliations
Kathrin Kostka
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, 45141 Essen, Germany
Viktoriya Sokolova
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, 45141 Essen, Germany
Aya El-Taibany
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
Benedikt Kruse
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, 45141 Essen, Germany
Daniel Porada
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
Natalie Wolff
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, 45141 Essen, Germany
Oleg Prymak
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, 45141 Essen, Germany
Michael C. Seeds
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
Matthias Epple
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, 45141 Essen, Germany
Anthony J. Atala
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
Among brain tumors, glioblastoma (GBM) is very challenging to treat as chemotherapeutic drugs can only penetrate the brain to a limited extent due to the blood–brain barrier (BBB). Nanoparticles can be an attractive solution for the treatment of GBM as they can transport drugs across the BBB into the tumor. In this study, normal and GBM organoids comprising six brain cell types were developed and applied to study the uptake, BBB penetration, distribution, and efficacy of fluorescent, ultrasmall gold nanoparticles (AuTio-Dox-AF647s) conjugated with doxorubicin (Dox) and AlexaFluor-647-cadaverine (AF647) by confocal laser scanning microscopy (CLSM), using a mixture of dissolved doxorubicin and fluorescent AF647 molecules as a control. It was shown that the nanoparticles could easily penetrate the BBB and were found in normal and GBM organoids, while the dissolved Dox and AF647 molecules alone were unable to penetrate the BBB. Flow cytometry showed a reduction in glioblastoma cells after treatment with AuTio-Dox nanoparticles, as well as a higher uptake of these nanoparticles by GBM cells in the GBM model compared to astrocytes in the normal cell organoids. In summary, our results show that ultrasmall gold nanoparticles can serve as suitable carriers for the delivery of drugs into organoids to study BBB function.
