Dokument

Summary:
ZUSAMMENFASSUNG In der vorliegenden Arbeit wurden innovative polymerische Vektoren, die für die Durchführung von Gentransfers entwickelt gewesen sind, vorgestellt. Hierbei richtete sich der besondere Akzent auf den Zusammenhang zwischen Struktur und Funktion sowohl aus physikalisch-chemischen als auch biologischen Blickpunkten. Zuerst wurden die für eine Transfektion relevanten Unterschiede von klassischen Vektoren mit hohem und niedrigem Verzweigungsgrad - PEI und PLL - unter alternierenden pH-Bedingungen von Krebsgewebe untersucht. Weiter wurde strukturelles Design für siRNA-Transfer auf Basis von PEG-PCL-PEI, einem multi-funktionellen selbst-assoziierenden ABC-Konstrukt, mit Betonung der Wichtigkeit der gesamten Hydrophilie-Lipophilie-Bilanz für effiziente Stilllegung der Genfunktion vorgeschlagen. Für Transport und Zustellung von DNA wurde ein neuer niedermolekularer diblock pDMAEMA-Abkömmling synthetisiert und charakterisiert, wonach der Vektor sich als effizient und geringfügig toxisch erwiesen hat. Der Zusammenhang zwischen pHEMA-Gehalt und Flexibilität der Polymerkette konnte mittels Dynamischer Simulation (MD) aufgeklärt werden. Die Besonderheiten zu thermodynamischen Aspekten von Polymer-DNA Bindung, die an die Glaspunkttemperatur (Tg) gekoppelt zu sein scheinen, wurden mittels ITC beobachtet. Sowohl die MD als auch die ITC- Methodiken lieferten neue Informationen zum Cargo-Carrier- Selbstorganisationsprozess in Lösung, welche wichtig in Bezug auf die Transfektionsleistung der Diblock-Copolymere sind.

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