Dokument: Aktives Targeting von Perfluorkarbon-Nanoemulsionen zur Ansteuerung humaner CD4(+) T-Zellen in vitro
| Titel: | Aktives Targeting von Perfluorkarbon-Nanoemulsionen zur Ansteuerung humaner CD4(+) T-Zellen in vitro | |||||||
| Weiterer Titel: | Active Targeting of Perfluorocarbon-Nanoemulsions for labelling human CD4(+) T-cells in vitro | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=69645 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250520-104713-3 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Wittke, Georgina Chiarella [Autor] | |||||||
| Dateien: |
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| Beitragende: | PD Dr. Sebastian Temme [Gutachter] Prof. Dr. Flögel, Ulrich [Gutachter] | |||||||
| Stichwörter: | Targeting; PFCs; Molekulare Kardiologie | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Das Immunsystem ist die wesentliche Barriere unseres Organismus zur Bekämpfung von Patho-genen. Zahlreiche Zellgruppen agieren in seinem Rahmen autonom durch ihre spezifischen Funktionen, wobei die interzellulären Interaktionen ebenso relevant für den Erfolg der Immun-abwehrfunktionen sind. Insbesondere die CD4(+) T-Zellen spielen eine zentrale Rolle in der Regu-lation der Immunantwort und der Vermeidung von Autoimmunreaktionen, da ihre Fähigkeit zum Klassentausch entscheidend für die Anpassung an unterschiedliche Pathogene und Umge-bungsbedingungen ist. Die Visualisierung von T-Zellen, insbesondere der CD4(+) T-Zellen, gewinnt daher im Kontext von Entzündungsprozessen und Autoimmunerkrankungen eine große klinische Bedeutung. Das Hauptziel der vorliegenden Arbeit liegt sowohl in der Optimierung der Visuali-sierung als auch in der Verbesserung der Markierungsspezifität von CD4(+) T-Zellen in der 19F-Magnetresonanztomographie (19F-MRT). Aufgrund ihrer Nichtinvasivität ist die MRT ein belieb-tes bildgebendes Verfahren für die medizinische Diagnostik. Der Einsatz nichttoxischer fluorba-sierter Kontrastmittel, in diesem Fall sind dies Perfluorkarbon-Nanoemulsionen (PFCs), soll diese in ihrer Genauigkeit und Effizienz ergänzen. Die Arbeit setzt sich aus mehreren Schritten zu-sammen, die sich auf die Untersuchung des passiven und aktiven Aufnahmeverhaltens von PFCs durch die Zielzellen konzentrieren. Im ersten Schritt wurde hierzu die passive PFC-Aufnahme durch Leukozyten untersucht. Dabei wurde geprüft, wie die Zellen die PFCs ohne zusätzliche Modifikationen aufnehmen. Auch der Einfluss einer PEGylierung der Partikel auf die Partikelin-korporation wurde analysiert. So konnte mit einer PEGylierung der Partikel von 20 mol% die Aufnahme durch phagozytisch aktive Zellen erfolgreich gehemmt werden. Innerhalb dieser Ar-beit wurde zudem auf Grundlage einer Biotin-Avidin-Kopplungsstrategie ein Targeting-System zur Markierung von CD4(+) T-Zellen mit biotinylierten PFCs etabliert. Einer der hierfür wichtigsten Schritte stellte die Biotinylierung der Nanopartikel dar, welche mittels anschließender MR-Bildgebung bestätigt wurde. Auch die Bindung biotinylierter Anti-CD4-Antikörper an die T-Zell-Oberfläche erwies sich als erfolgreich. Im aktiven Targeting der PFCs ließ sich eine präferierte Partikelinkorporation biotinylierter PFCs durch CD4(+) T-Zellen darstellen und die Biotin-Avidin-Kopplung zwischen Zellen und PFCs bestätigen.
Insgesamt liefert diese Arbeit somit wichtige Erkenntnisse zur Optimierung bildgebender Verfah-ren und zur zielgerichteten Darstellung spezifischer Zellpopulationen. Für zukünftige Projekte wird eine Überarbeitung der Targeting-Strategie empfohlen, um eine noch präzisere und spezifi-schere Bindung der Partikel an CD4(+) T-Zellen zu erreichen. Die gewonnenen Erkenntnisse kön-nen langfristig zur Verbesserung diagnostischer und therapeutischer Ansätze beitragen, indem sie eine genauere Visualisierung von Immunzellen ermöglichen.The immune system is the essential barrier of our organism to combat pathogens. Numerous cell groups act autonomously within its framework through their specific functions, whereby the intercellular interactions are just as relevant for the success of immune defence functions. CD4(+) T cells in particular play a central role in the regulation of the immune response and the avoidance of autoimmune reactions, as their ability to switch classes is decisive for the adaptation to different pathogens and environmental conditions. Therefore, the visualisation of T cells, especially CD4(+) T cells, is of great clinical importance in the context of inflammatory processes and autoimmune diseases. The main aim of the present work is to optimise the visualisation and to improve the labelling specificity of CD4(+) T cells in 19F magnetic resonance imaging (19F MRI). Due to its non-invasiveness, MRI is a popular imaging technique for medical diagnostics. The use of non-toxic fluorine-based contrast agents, in this case perfluorocarbon nanoemulsions (PFCs), is intended to complement it in terms of accuracy and efficiency. The work consists of several steps which focus on the investigation of the passive and active uptake behaviour of PFCs by the target cells. In the first step, passive PFC uptake by leukocytes was investigated. This involves examining how the cells take up the PFCs without additional modifications. The influence of PEGylation of the particles on particle incorporation by the leukocytes was also analysed. Particle-PEGylation of 20 mol% suppressed the uptake by phagocytically active cells successfully. Within this work, a targeting system for labelling CD4(+) T cells with biotinylated PFCs was also established using a biotin-avidin coupling strategy. The biotinylation of the nanoparticles was one of the most important steps in this process, which was confirmed by subsequent MR imaging. The binding of biotinylated anti-CD4 antibodies to the T-cell surface also proved to be successful. In the active targeting of PFCs, a preferential particle incorporation of biotinylated PFCs by CD4(+) T cells was demonstrated, thus confirming the biotin-avidin interaction between cells and PFCs. In summary, this work provides important insights into the optimisation of imaging techniques and the targeted imaging of specific cell populations. For future projects, a revision of the targeting strategy is recommended in order to achieve even more precise and specific binding of the particles to CD4(+) T cells. In the long term, the knowledge gained can contribute to the improvement of diagnostic and therapeutic approaches by enabling more precise visualisation of immune cells. | |||||||
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| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Bezug: | 10/2021 - 04/25 | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 20.05.2025 | |||||||
| Dateien geändert am: | 20.05.2025 | |||||||
| Promotionsantrag am: | 12.01.2025 | |||||||
| Datum der Promotion: | 24.04.2025 |
