Dokument: The interaction of graphene quantum dots with human cells
Titel: | The interaction of graphene quantum dots with human cells | |||||||
Weiterer Titel: | Die Interaktion von Graphen-Quantendots mit menschlichen Zellen | |||||||
URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=54208 | |||||||
URN (NBN): | urn:nbn:de:hbz:061-20200924-110015-8 | |||||||
Kollektion: | Dissertationen | |||||||
Sprache: | Englisch | |||||||
Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
Medientyp: | Text | |||||||
Autor: | Fasbender, Stefan [Autor] | |||||||
Dateien: |
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Beitragende: | Prof. Dr. Heinzel, Thomas [Gutachter] Prof. Dr. Haas, Rainer [Gutachter] | |||||||
Stichwörter: | Graphene quantum dots, nanoparticles, toxicity | |||||||
Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 530 Physik | |||||||
Beschreibung: | Graphene quantum dots (GQDs) consist of one or a few layers of graphene. They are used in biomedical research not only for drug delivery applications, but also for long term and deep tissue imaging, cancer diagnostics and intracellular sensing. All of these applications require profound knowledge about the effect of GQDs on the cells. This thesis deals with the uptake dynamics of the GQDs into different cells, the intracellular distribution of the GQDs and the transcriptomic response of the cells to GQDs.
First, we established a reliable and reproducible preparation process based on the pyrolysis of citric acid. The as prepared GQDs were characterized by fluorescence spectroscopy, ultraviolet-visible spectrophotometry, X-ray photoelectron spectroscopy, high resolution transmission electron microscopy and Raman spectroscopy. Then we studied the uptake dynamics of GQDs into primary human blood cells for a period of 36 hours. We observed for all cell types studied an approximately linear time- and concentration-dependent uptake with a significantly greater uptake into monocytes and granulocytes in comparison to lymphocytes. The effect of the GQDs on the viability of the cells was rather low with a measured viability of 90% after an exposure time of 36 hours. The next set of experiments concentrated on the intracellular distribution and uptake of GQDs into different breast cancer models. A three times higher uptake into estrogen receptor positive, progesterone receptor positive, HER2 negative MCF-7 cells was observed compared to MDA-MB-231 cells as an example for triple negative breast cancer and MCF-10A cells as a model for non-tumorigenic mammary epithelial cells. It was demonstrated for all three cell types that the GQDs accumulate near the nucleus inside the endolysosomal system. Furthermore, the penetration of GQDs into murine precision-cut mammary tumor slices was studied, where a constant uptake into the depth of the tissue and no increase of apoptotic or necrotic cells was found. Finally, we examined the effect of GQDs on the transcriptome of primary human CD34+ hematopoietic stem cells. Only one of the 20 800 recorded gene expressions, namely the selenoprotein W, 1, was changed by the GQDs in direct comparison to CD34+ hematopoietic stem cells cultivated without GQDs. Only a meta analysis revealed that the expression of 1171 genes was weakly affected, taking into account the more prominent changes just by the cell culture. Eight corresponding, weakly affected signaling pathways were identified, which include, but are not limited to, the triggering of apoptosis. | |||||||
Lizenz: | Urheberrechtsschutz | |||||||
Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Physik » Physik der kondensierten Materie | |||||||
Dokument erstellt am: | 24.09.2020 | |||||||
Dateien geändert am: | 24.09.2020 | |||||||
Promotionsantrag am: | 12.03.2020 | |||||||
Datum der Promotion: | 25.08.2020 |