Dokument: Optimierung der "stealth"-Eigenschaften von Perlfuorkarbon-Nanoemulsionen im Hinblick auf ein aktives Targeting von neutrophilen Granulozyten

Titel:

Optimierung der "stealth"-Eigenschaften von Perlfuorkarbon-Nanoemulsionen im Hinblick auf ein aktives Targeting von neutrophilen Granulozyten

Weiterer Titel:

Optimization of the "stealth"-properties of per fluorocarbon-nanoemulsions to improve the active targeting to human neutrophil granulocytes

URL für Lesezeichen:

https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=74244

URN (NBN):

urn:nbn:de:hbz:061-20260824-152054-6

Kollektion:

Dissertationen

Sprache:

Deutsch

Dokumententyp:

Wissenschaftliche Abschlussarbeiten » Dissertation

Medientyp:

Text

Autor:

Rosentrit, Vanessa [Autor]

Dateien:

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Dateien vom 16.08.2026 / geändert 16.08.2026

Beitragende:

Prof. Dr. rer. nat. Temme, Sebastian [Gutachter]
Prof. Dr. rer. nat. Flögel, Ulrich [Gutachter]

Stichwörter:

Aktives Targeting; PFCs; stealth; Molekulare Kardiologie

Dewey Dezimal-Klassifikation:

600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit

Beschreibungen:

Die Bildgebung spielt in der Medizin eine zentrale Rolle, da sie maßgeblich die Diagnose, Therapie und Prognose beeinflusst. Insbesondere die spezifische Darstellung von Entzündungsprozessen stellt weiterhin eine Herausforderung dar. Eine in der Klinik etablierte nicht-invasive Bildgebungsmodalität stellt die Magnetresonanztomographie (MRT) dar, welche eine hervorragende Darstellung von Weichgeweben ermöglicht, aber keine ionisierte Strahlung benötigt. Die Detektion von Entzündungsprozessen mittels MRT ist bei Verwendung konventioneller anatomischer Bildgebungssequenzen nur eingeschränkt möglich. Jedoch stellt die Beladung von phagozytischen Immunzellen mit Perfluorkarbon Nanoemulsionen in diesem Zusammenhang einen vielversprechenden Ansatz dar, da Fluor im menschlichen Körper nahezu nicht vorkommt und somit eine hochspezifische und nahezu hintergrundfreie Visualisierung mittels 19F-MRT möglich ist. Bereits 2008 konnte Flögel et. al. im Mausmodell eines Myokardinfarktes durch intravenös injizierte Perfluorkarbon Nanoemulsionen entzündliche Prozesse durch Aufnahme von Monozyten mittels kombinierter 1H/19F-MRT darstellen. Der Fokus dieser Arbeit lag auf der gezielten Bildgebung neutrophiler Granulozyten, da sie zu den ersten Immunzellen gehören, die in das inflammatorische Gewebe migrieren. Eine frühzeitige und spezifische Visualisierung dieser Immunzellpopulation eröffnet daher neue diagnostische Möglichkeiten. Ziel dieser Arbeit war die Optimierung des Targetings von Perfluorkarbon-Nanoemulsionen (PFCs) zur selektiven Darstellung von neutrophilen Granulozyten. Zum Targeting von neutrophilen Granulozyten wurde ein spezifisch an CD177 bindendes Peptid (hN-Peptid) an die PFCs gekoppelt. Zur Reduktion der unspezifischen Aufnahme durch Monozyten und
Makrophagen wurden die PFCs zusätzlich entweder PEGyliert oder mit einem CD47 Peptid funktionalisiert. Die PEGylierung der PFCs führte zu einer verminderten unspezifischen Aufnahme, insbesondere in Monozyten und damit zu einer verbesserten Spezifität. Das aktive Targeting mittels hN-Peptid steigerte die Aufnahme in neutrophilen Granulozyten. Jedoch wurde durch zusätzliche PEGylierung nicht nur die unspezifische, sondern auch die spezifische Aufnahme reduziert. CD47 ist dafür bekannt ein „don’t eat me“-Signal zu vermitteln. Die CD47 Funktionalisierung zeigte eine moderate Reduktion der monozytären Aufnahme bei gleichzeitig geringem Effekt auf neutrophile Granulozyten, wobei zudem eine donorspezifische Variabilität der SIRPa-Expression beobachtet wurde. Da SIRPa als Rezeptor für CD47 fungiert, könnte die Variabilität die unterschiedlich ausgeprägten Effekte
der CD47-Funktionalisierung erklären. Eine Kombination aus CD47 und aktivem Targeting mittels hN-Peptid führte entgegen der Erwartung nicht zu einer weiteren Reduktion der monozytären Aufnahme. Stattdessen zeigte sich eine teilweise erhöhte Aufnahme in neutrophilen Granulozyten, was auf komplexe Wechselwirkungen der Modifikationen hinweist. Insgesamt liefern die Ergebnisse dieser Arbeit wichtige Erkenntnisse zur Optimierung von PFC-Nanoemulsionen für die zellspezifische Bildgebung. Für die Zukunft bedarf es eine weitere Optimierung der Oberflächenmodifikation, um eine noch spezifischere und gezieltere
Darstellung neutrophiler Granulozyten ermöglichen. Dies könnte in der Medizin langfristig zur Verbesserung der Diagnostik entzündlicher Erkrankungen beitragen.

Imaging plays a central role in medicine, as it significantly influences diagnosis, therapy and prognosis. In particular, the specific visualization of inflammatory processes remains a major
challenge. An established non-invasive imaging modality is magnetic resonance imaging (MRI) which provides excellent soft tissue contrast, but does not require ionizing radiation. However,
the detection of inflammatory processes using conventional anatomical MRI sequences is limited. In this context, immune cells loaded with perfluorocarbon nanoemulsions (PFCs) represent a promising approach, as fluorine in virtually absent in the human body, enabling specific and nearly background-free imaging using 19F-MRI. In 2008, Flögel et al. demonstrated in a mouse model of myocardial infarction that inflammatory processes can be visualized using intravenously administered perfluorocarbon nanoemulsions, which are taken up by monocytes and detected via combined 1H/19F-MRI. The focus of this work was the targeted imaging of
neutrophil granulocytes, as they are among the first immune cells to migrate into inflamed tissue. Early and specific visualization of this immune cell population therefore offers new diagnostic opportunities. The aim of this study was to optimize the targeting of perfluorocarbon nanoemulsions (PFCs) for the selective visualization of neutrophil granulocytes. For this purpose, a CD177-specific peptide (hN-peptide) was conjugated to the PFCs. To reduce the nonspecific uptake by monocytes and macrophages, the PFCs were additionally either PEGylated or functionalized with a CD47-peptide. PEGylation of PFCs led to a reduction in unspecific cellular uptake, particularly in monocytes, thereby improving specificity. Active targeting using neutrophilspecific hN-peptide enabled a selective increase in uptake by neutrophil granulocytes.
However, additional PEGylation reduced not only unspecific but also specific uptake. CD47 is known to mediate a “don’t eat me”-signal. CD47-functionalization led to moderate reduction in
monocyte uptake, while only minor effects were observed in neutrophils. Furthermore, a donordependent variability in SIRPa-expression was observed. As SIRPa- functions as the receptor
of CD47, this variability may explain the heterogeneity in the observed effects of CD47. Unexpectedly, a combination of CD47 and active targeting via hN-peptide did not lead to a further reduction in monocyte uptake. Instead, a partially increased uptake in neutrophil granulocytes was observed, suggesting complex interactions between the different surface modifications. Overall, the results of this study provide important insights into optimization of PFC nanoemulsions for cell-specific imaging. Further refinement of surface modification strategies will be necessary to achieve more specific and targeted imaging of neutrophil granulocytes. In
the long term, this approach may contribute to improve diagnostic strategies for inflammatory diseases in medicine.

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Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz

Fachbereich / Einrichtung:

Medizinische Fakultät

Dokument erstellt am:

24.08.2026

Dateien geändert am:

24.08.2026

Promotionsantrag am:

01.05.2026

Datum der Promotion:

11.08.2026

Heinrich-Heine-Universität Düsseldorf

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