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 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.
Guillot-Nieckowski
Marine
M
Laboratorium für Organische Chemie, ETH-Zürich, Hönggerberg, HCI, 8093 Zürich, Switzerland.
Joester
Derk
D
Stöhr
Meike
M
Losson
Myriam
M
Adrian
Marc
M
Wagner
Bjoern
B
Kansy
Manfred
M
Heinzelmann
Harry
H
Pugin
Raphaël
R
Diederich
François
F
Gallani
Jean-Louis
JL
D002412:Cations / Q000737:chemistry; D020285:Cryoelectron Microscopy; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D004563:Electrochemistry / Q000379:methods; D004705:Endocytosis; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006863:Hydrogen-Ion Concentration; D046529:Microscopy, Electron, Transmission; D020527:Microscopy, Scanning Probe; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014162:Transfection / Q000295:instrumentation* / Q000379:methods
D002412:Cations; D050091:Dendrimers; D004247:DNA