Self-assembly, DNA Complexation, and pH Response of Amphiphilic Dendrimers for Gene Transfection

Cationic lipids and polymers are routinely used for cell transfection, and a variety of structure−activity relation data have been collected. Few studies, however, focus on the structural aspects of self-assembly as a crucial control parameter for gene delivery. We present here the observations coll...

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Veröffentlicht in:Langmuir 2007-01, Vol.23 (2), p.737-746
Hauptverfasser: Guillot-Nieckowski, Marine, Joester, Derk, Stöhr, Meike, Losson, Myriam, Adrian, Marc, Wagner, Bjoern, Kansy, Manfred, Heinzelmann, Harry, Pugin, Raphaël, Diederich, François, Gallani, Jean-Louis
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Sprache:eng
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Zusammenfassung:Cationic lipids and polymers are routinely used for cell transfection, and a variety of structure−activity relation data have been collected. Few studies, however, focus on the structural aspects of self-assembly as a crucial control parameter for gene delivery. We present here the observations collected for a set of cationic dendritic amphiphiles based on a stiff tolane core (1 − 4) that are built from identical subunits but differ in the number and balance of their hydrophobic and cationic hydrophilic moieties. We established elsewhere that vectors 3 and 4 have promising transfection properties. Scanning probe microscopy (AFM, STM), cryo-transmission electron microscopy (cryo-TEM), and Langmuir techniques provide insight into the self-assembly properties of the molecules under physiological conditions. Furthermore, we present DNA and pH “jump” experiments where we study the response of Langmuir films to a sudden increase in DNA concentration or a drop in pH. We find that the primary self-assembly of the amphiphile is of paramount importance and influences DNA binding, serum sensitivity, and pH response of the vector system.
ISSN:0743-7463
1520-5827
DOI:10.1021/la0624891