Self-assembly, DNA complexation, and pH response of amphiphilic dendrimers for gene transfection.
Fiche publication
Date publication
janvier 2007
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GALLANI Jean-Louis
Tous les auteurs :
Guillot-Nieckowski M, Joester D, Stohr M, Losson M, Adrian M, Wagner B, Kansy M, Heinzelmann H, Pugin R, Diederich F, Gallani JL
Lien Pubmed
Résumé
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.
Référence
Langmuir. 2007 Jan 16;23(2):737-46.