Monomolecular condensation of DNA by cationic detergents

Controlling the size of condensed DNA particles is a key determinant for their diffusion in vivo as well as for gene delivery to target cells. Towards this goal, DNA molecules were compacted individually by cationic thiol‐detergents into discrete nanometric entities. These particles were then stabilized by air‐induced dimerization of the detergent into a disulfide lipid on the template DNA. Using a tetradecane–cysteine–ornithine (C14COrn) detergent, a solution of 5.5 Kb plasmid DNA was thus converted into a monodisperse population of 35‐nm particles. The stability of the complexes, as well as their size, morphology and transfection efficiencies were investigated. Surprisingly, the electrophoretic mobility of the quasi‐neutral condensed DNA was found higher than that of the extended DNA polyanion. The diameters of particles resulting from the condensation of DNA of various sizes was measured by dynamic light scattering and found to vary as the cubic root of the DNA size. In an attempt to extend their biodistribution and to target tumour cells, we have prepared folate–poly(ethylene oxide)‐coated particles that were shown to bind to the cell‐surface folate receptor. Copyright © 2003 Society of Chemical Industry