Dokument: Gold Nanoparticles as Drug Delivery Systems for Brain Cancer Therapy
| Titel: | Gold Nanoparticles as Drug Delivery Systems for Brain Cancer Therapy | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=56964 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20210728-105738-8 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Giesen, Beatriz [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Christoph Janiak [Gutachter] PD Dr. Kahlert, Ulf Dietrich [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 540 Chemie | |||||||
| Beschreibung: | Glioblastoma (GB) is the most common and most aggressive type of primary brain tumor with an average two-year survival rate of patients after consensus therapy consisting of surgical gross resection, followed by adjuvant chemo- and radiotherapy. The reason for its occurrence, invasive behavior to other healthy tissues and constant recurrence upon surgical resection can be attributed to the existence of an aggressive subpopulation of tumor cells called GB stem cells (GSCs). GSCs, characterized by the expression of neural stem cell markers and their capacity of self-renewal, possess very efficient and augmented DNA repair and protection programs, translating to a clinically unwanted therapy resistance of the tumor. Even though promising pharmacotherapies with great potential to target GSCs have been identified, their desired bioavailability inside the target site is still limited due to cellular defense mechanisms of GSCs. In this work, gold nanoparticles (Au NPs) were designed to serve as drugs carriers able to penetrate GSCs and enhance the stability and solubility of therapeutics.
Due to their biocompatibility, straight-forward functionalization and unique optical properties, Au NPs are suitable candidates to improve GB therapy. In the initial part of this project, the optimal synthesis parameters and ligand composition of Au NPs needed to achieve a high internalization degree into GSCs was investigated. Au NPs were synthesized in a fast microwave-assisted reaction using the polymer polyethylenimine (PEI) as a reducing agent for the Au(III) precursor, a stabilizer against NP agglomeration and a platform for subsequent gene or drug conjugation. In order to track the Au NPs inside the cells, the fluorescent marker fluorescein isothiocyanate (FITC) was bound to the NP surface. The fluorescence emitted by the AuPEI-FITC NPs allowed their quantification after incubation into the cells, as well as a differentiation between cell surface-bound and internalized NPs. In vitro experiments with GSCs indicated no apparent cytotoxicity for AuPEI-FITC NPs. The maximal NP internalization was 61%, depending on the NP synthesis method and the cell type tested. Following these findings, the ability of Au NPs to load and deliver the promising clinical drug candidate CB839 into GSCs was studied. First, five different Au NPs with polymeric and non-polymeric capping ligands were synthesized and reacted with CB839 to form an Au-ligand-CB839 conjugate. The drug loading efficiency (DLE) for each NP type was evaluated using high-performance liquid chromatography, accompanied by qualitative microscopic and spectroscopic investigations. Despite the chemical inertness and poor-water solubility of CB839, Au-polymer NPs reached a DLE of up to 12%. Assessments in GSC in vitro models showed an increased therapeutic potential of the nanodelivered CB839, compared to CB839 alone. Optical assessment proved the successful high rate of intracellular penetration of Au-CB839 NPs into GSCs. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Chemie » Anorganische Chemie und Strukturchemie | |||||||
| Dokument erstellt am: | 28.07.2021 | |||||||
| Dateien geändert am: | 28.07.2021 | |||||||
| Promotionsantrag am: | 11.05.2021 | |||||||
| Datum der Promotion: | 02.07.2021 |
