Dokument

Zusammenfassung:
Magnetische Nanopartikel finden eine breite biomedizinische Anwendung als Biosensoren und als KM in der Bildgebung, ferner werden sie eingesetzt, wenn eine gezielte Wirkstoffabgabe erreicht werden soll. Außerdem spielt die molekulare MRT eine wichtige Rolle bei der Tumordiagnostik. Die schnelle Entwicklung der Nanotechnologie und die zunehmende Anzahl unterschiedlicher Nanomaterialien, die aufgrund ihrer besonderen physikalischen Eigenschaften und der guten Biokompatibilität metallischer und anorganischer Nanopartikel zum Einsatz kommen, führen dazu, dass immer mehr neue Nanostrukturen in Kontakt mit Mensch und Umwelt kommen. Eisenoxidbasierte MRT-Kontrastmittel umfassen SPIO-Partikel. Sie werden klinisch bei der Leberbildgebung eingesetzt und vom mononukleären Phagocytensystem aufgenommen. Außerdem können Zellen mit SPIO-Partikeln markiert und als In-vivo-Kontrastmarker für die MRT-Bildgebung verwendet werden. Bei der Zellmarkierungstechnik sollen unterschiedliche Parameter optimiert werden, z. B. Größe, Beschichtung und Dosis der Partikel sowie die Inkubationszeit. Derzeit liegt deshalb der Fokus vieler Studien auf modifizierten und unterschiedlich beschichteten SPIO-Partikeln. In der vorliegenden Arbeit wurden 2 verschiedene SPIO-Formulierungen getestet und es wurde die Aufnahme der SPIO-Partikel in unterschiedliche Zelltypen – murine Makrophagen, humane leukämische Monocyten sowie humane mesenchymale Stammzellen – untersucht. Viele Forscher versuchen eine spezifische Markierung durch modifizierte SPIO-Partikel zu erreichen. Hierbei gibt es allerdings starke Bedenken, was die Biosicherheit solcher Partikel angeht. In dieser Arbeit wurden SPIO-Formulierungen verwendet, die ohne Modifizierungen und bei einer relativ niedrigen Konzentration gute Ergebnisse erzielten. Phagocytierende Zellen wurden mit 2,79 µg Fe/ml und 27,92 µg Fe/ml inkubiert. Nach 12 h lag der Eisengehalt pro J774A.1-Zelle bei 13,77 ± 0,5 pg. Bei THP-1-Zellen konnte eine geringere Aufnahme beobachtet werden, das intrazelluläre Eisen betrug 24 h nach der Markierung 9,84 ± 1,6 pg Fe pro Zelle. Aufgrund ihrer hervorragenden Eigenschaften besitzen Stammzellen ein großes Potential in der regenerativen Medizin. Die Mechanismen, die der Transplantation von Stammzellen in ein Target-Organ zugrunde liegen, sind jedoch noch nicht verstanden. Nach einer Markierung der Zellen mit SPIO-Partikeln kann die Migration der Zellen nach der Transplantation mittels MRT beobachtet werden. In dieser Arbeit wurden humane mesenchymale Stammzellen mit SPIO, aber ohne die Hilfe eines Transfektionsagens markiert. Bei der Markierung der Stammzellen wurde mit einer höheren Konzentration von SPIO-Partikeln (25 µg Fe/ml) im Vergleich zur Markierung phagocytierender Zellen begonnen. Die Markierung von hMSC war effizient. Eine der wichtigsten Eigenschaften von Stammzellen ist ihre Differenzierungsfähigkeit, die in dieser Arbeit ebenfalls untersucht wurde. Die Markierung mit SPIO-Partikeln beeinflusste das Differenzierungspotential von hMSC zu Osteoblasten und Adipocyten nicht. Um herauszufinden, ob SPIO-Partikel einen T2-verstärkenden Effekt haben, wurden die T1- und T2-Werte unterschiedlicher KM-Lösungen bei 7 T gemessen und das r2/r1-Verhältnis berechnet. Sowohl 1/T1 als auch 1/T2 nahmen linear mit der SPIO-Konzentration zu. Für das untersuchte eisenoxidhaltige KM wurde ein r2-Wert von 178 mM-1s-1 in Wasser ermittelt. Das Verhältnis r2/r1 lag bei 66 (gemessen in Wasser). Mit Erhöhung der Viskosität nahm auch r2 zu, sodass in Mausplasma ein r2-Wert von 184,6 mM-1s-1 bestimmt wurde. Die getesteten SPIO-Partikel wiesen ein Verhältnis r2/r1 von 108,6 bei 7 T auf (in Mausplasma, gemessen bei RT). Die bei 7 T zu erwartenden höheren r2-Werte im Vergleich zu einem aus der Literatur bekannten Wert von Ferucarbotran (diente als Referenz-KM), gemessen bei 4,7 T, konnten nicht beobachtet werden, was an den unterschiedlichen Temperaturen und einer möglichen Feldinhomogenität bei den Messungen liegen könnte.

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