Structure of the Electrostatic Complex of DNA with Cationic Dendrimer of Intermediate Generation: The Role of Counterion Entropy

Abstract

Polyamidoamine (PAMAM) dednrimer bearing a well-defined number of amine groups can be protonated under physiological or acidic condition to generate the macrocations capable of forming electrostatic complex (called “dendriplex”) with DNA for gene delivery. Using small-angle X-ray scattering (SAXS) and small angle neutron scattering (SANS), here we constructed the morphological map of the complex of DNA with PAMAM dendrimer of generation four (G4) in terms of the dendrimer charge density and the nominal N/P ratio given by the feed molar ratio of dendrimer amine group to DNA phosphate group. With the increase of dendrimer charge density under a given nominal N/P ratio, the structure was found to transform from square columnar phase (in which the DNA chains packed in square lattice were locally straightened) to hexagonally-packed DNA superhelices (in which the DNA chains organizing in a hexagonal lattice twisted moderately into superhelices) and finally to beads-on-string structure (in which DNA wrapped arou...