Self-assembling polycations for gene delivery: Effects of polymer structure and environmental pH

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...

Full description

Saved in:
Bibliographic Details
Main Author: Samsonova, Olga
Contributors: Kissel, Thomas (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Published: Philipps-Universität Marburg 2012
Online Access:PDF Full Text
Tags: Add Tag
No Tags, Be the first to tag this record!
Table of Contents: SUMMARY In this thesis, novel polycationic vectors for therapeutic gene delivery were introduced with the focus on structure-function relationship in both physicochemical and biological aspects. First the transfection related differences of classical vectors with high and low branching grade and charge density: PEI and PLL, were examined under pH-alternating tumor tissue conditions. Further structural design for siRNA delivery was proposed on base of PEG-PCL-PEI multifunctional self-assembly ABC-construct, showing the importance of total hydrophilic-lipophilic balance for efficient gene silencing performance. For DNA delivery a new low molecular weight di-block pDMAEMA derivative was synthesized and characterized, proving it to be a low toxic and efficient vector. The relationship between pHEMA-content and polymer chain flexibility was assessed via molecular dynamics simulation (MD). The thermodynamic polymer-DNA binding characteristics, monitored via ITC, appeared to depend on glass transition temperatue (Tg). The use of both MD and ITC methodologies provided new information on the cargo-carrier self-assembly process in solution, relevant to transfection performance of diblock-copolymers.