Bioconjugate Chemistry 2008-12-01

Development and characterization of new cyclodextrin polymer-based DNA delivery systems.

Virginie Burckbuchler, Véronique Wintgens, Christian Leborgne, Sophie Lecomte, Nadine Leygue, Daniel Scherman, Antoine Kichler, Catherine Amiel

Index: Bioconjug. Chem. 19(12) , 2311-20, (2008)

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Abstract

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.