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Article

The Application of Ultrasmall Gold Nanoparticles (2 nm) Functionalized with Doxorubicin in Three-Dimensional Normal and Glioblastoma Organoid Models of the Blood–Brain Barrier

by
Kathrin Kostka
1,*,
Viktoriya Sokolova
1,
Aya El-Taibany
2,
Benedikt Kruse
1,
Daniel Porada
2,
Natalie Wolff
1,
Oleg Prymak
1,
Michael C. Seeds
2,
Matthias Epple
1 and
Anthony J. Atala
2,*
1
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, 45141 Essen, Germany
2
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
*
Authors to whom correspondence should be addressed.
Molecules 2024, 29(11), 2469; https://doi.org/10.3390/molecules29112469
Submission received: 5 April 2024 / Revised: 28 April 2024 / Accepted: 1 May 2024 / Published: 24 May 2024
(This article belongs to the Special Issue Materials Chemistry in Europe)
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Abstract

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.
Keywords: gold; nanoparticles; doxorubicin; organoids; glioblastoma; blood–brain barrier; drug delivery gold; nanoparticles; doxorubicin; organoids; glioblastoma; blood–brain barrier; drug delivery

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MDPI and ACS Style

Kostka, K.; Sokolova, V.; El-Taibany, A.; Kruse, B.; Porada, D.; Wolff, N.; Prymak, O.; Seeds, M.C.; Epple, M.; Atala, A.J. The Application of Ultrasmall Gold Nanoparticles (2 nm) Functionalized with Doxorubicin in Three-Dimensional Normal and Glioblastoma Organoid Models of the Blood–Brain Barrier. Molecules 2024, 29, 2469. https://doi.org/10.3390/molecules29112469

AMA Style

Kostka K, Sokolova V, El-Taibany A, Kruse B, Porada D, Wolff N, Prymak O, Seeds MC, Epple M, Atala AJ. The Application of Ultrasmall Gold Nanoparticles (2 nm) Functionalized with Doxorubicin in Three-Dimensional Normal and Glioblastoma Organoid Models of the Blood–Brain Barrier. Molecules. 2024; 29(11):2469. https://doi.org/10.3390/molecules29112469

Chicago/Turabian Style

Kostka, Kathrin, Viktoriya Sokolova, Aya El-Taibany, Benedikt Kruse, Daniel Porada, Natalie Wolff, Oleg Prymak, Michael C. Seeds, Matthias Epple, and Anthony J. Atala. 2024. "The Application of Ultrasmall Gold Nanoparticles (2 nm) Functionalized with Doxorubicin in Three-Dimensional Normal and Glioblastoma Organoid Models of the Blood–Brain Barrier" Molecules 29, no. 11: 2469. https://doi.org/10.3390/molecules29112469

APA Style

Kostka, K., Sokolova, V., El-Taibany, A., Kruse, B., Porada, D., Wolff, N., Prymak, O., Seeds, M. C., Epple, M., & Atala, A. J. (2024). The Application of Ultrasmall Gold Nanoparticles (2 nm) Functionalized with Doxorubicin in Three-Dimensional Normal and Glioblastoma Organoid Models of the Blood–Brain Barrier. Molecules, 29(11), 2469. https://doi.org/10.3390/molecules29112469

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