Development and characterization of new cyclodextrin polymer-based DNA delivery systems.
In this study, we investigated whether a cyclodextrin polymer (polybetaCD) complexed with cationic adamantyl derivatives (Ada) could be used as a vector for gene delivery. DNA compaction as a function of adamantyl/DNA phosphate ratio (A/P) by this new class of vector was demonstrated using surface enhanced Raman spectroscopy, zeta potential measurements, and DNA retardation assays. Transfection data highlight the relationship between in vitro gene delivery efficiency and the combination of several physical properties of the polybetaCD/Ada/DNA polyplexes, including cationic polar headgroup valency and chemical structure of the spacer arm of Ada connectors, the adamantyl/DNA phosphate ratio (A/P) of the polybetaCD/Ada/DNA polyplexes, and the ionic strength of the medium. Finally, when associating the best formulation with a fusogenic peptide, we reached transfection levels which were of the same order as those obtained with DOTAP.
Burckbuchler
Virginie
V
Institut de Chimie des Materiaux Paris Est, Systemes Polymeres Complexes, Universite Paris 12 Val de Marne, CNRS, 2-8 rue Henri Dunant, 94320 Thiais, France.
Wintgens
Véronique
V
Leborgne
Christian
C
Lecomte
Sophie
S
Leygue
Nadine
N
Scherman
Daniel
D
Kichler
Antoine
A
Amiel
Catherine
C
D045744:Cell Line, Tumor; D002482:Cellulose / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D003188:Composite Resins / Q000737:chemistry; D003505:Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000235:genetics* / Q000378:metabolism*; D005453:Fluorescence; D018014:Gene Transfer Techniques; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D033363:Neutron Diffraction; D009994:Osmolar Concentration; D053838:Scattering, Small Angle; D013059:Spectrum Analysis, Raman; D013499:Surface Properties; D014162:Transfection
D003188:Composite Resins; D003505:Cyclodextrins; C529459:adamant composite resin; C041953:cyclodextrin polymer; D002482:Cellulose; D004247:DNA