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

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• 作者：Marine Guillot-Nieckowski ; Derk Joester ; Meike Stö ; hr ; Myriam Losson ; Marc Adrian ; Bjoern Wagner ; Manfred Kansy ; Harry Heinzelmann ; Rapha&euml ; l Pugin ; Franç ; ois Diederich ; Jean-Louis Gallani
• 刊名：Langmuir
• 出版年：2007
• 出版时间：January 16, 2007
• 年：2007
• 卷：23
• 期：2
• 页码：737 - 746
• 全文大小：801K
• 年卷期：v.23,no.2(January 16, 2007)
• ISSN：1520-5827

文摘

Cationic lipids and polymers are routinely used for cell transfection, and a variety of structure-activity relationdata have been collected. Few studies, however, focus on the structural aspects of self-assembly as a crucial controlparameter for gene delivery. We present here the observations collected for a set of cationic dendritic amphiphilesbased on a stiff tolane core (1-4) that are built from identical subunits but differ in the number and balance of theirhydrophobic and cationic hydrophilic moieties. We established elsewhere that vectors 3 and 4 have promising transfectionproperties. Scanning probe microscopy (AFM, STM), cryo-transmission electron microscopy (cryo-TEM), and Langmuirtechniques 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 increasein DNA concentration or a drop in pH. We find that the primary self-assembly of the amphiphile is of paramountimportance and influences DNA binding, serum sensitivity, and pH response of the vector system.