Analytical model study of Dendrimer-DNA complexes

Khawla Qamhieh,* Tommy Nylander, ^† and Marie-Louise Ainalem^†

* Physics Department, College of Science and Technology, Al-Quds University,Jerusalem, Palestine

^† Physical Chemistry 1, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden

E-mail: khawlaqa@yahoo.com

Abstract

The general trend in the modern development of biology, pharmaceutics, and medicine is closely related to the utilization of nanotechnology. One of the examples is in gene therapy where DNA has to be delivered into a cell in order to for example correct the genetic defects of damaged sites. Here the challenge is to be able to transport DNA, which generally is a very large, stiff and therefore bulky PE, through the cell walls. This can be achieved by condensing DNA with an oppositely charged specimen, such as cationic surfactants or PEs. In recent years DNA condensation by using different surfactants like CTAB or DODAB, histones, as well as synthetic poly(amido amine) ( PAMAM) dendrimers, polylysine, or poly(ethylene imine) (PEI) specimen has been studied extensively as a way of replacing viral vectors as gene carriers for in vivo transfer.

Dendrimers are globular nanostructures that can be highly charged, which makes them very efficient DNA condensing agents, with electrostatic forces stabilizing the formed complexes. The structure is very sensitive to the ionic strength where a more extended structure is formed at low amounts of salt due to the intramolecular electrostatic repulsion. Dendrimers of fourth generation (G4) have been shown to be soft and flexible containing a dense core.

The interaction between cationic poly(amido amine) (PAMAM) dendrimers of generation 4 and double stranded DNA has been investigated for two different lengths of DNA;  2000 basepairs (bp) (680 nm contour length) and 4331bp (1472.5 nm contour length) using a theoretical model developed by Schiessel. In this model, which we adopted, the complexes are considered to be formed by positively charged hard spheres (macroions). For the shorter DNA, the estimated optimal wrapping length is »14.2 nm, whereas the estimated wrapping length for the longer DNA in the presence of dendrimers is shorter (»9.87 nm). The estimated maximum number ( ) of dendrimers per discrete aggregate containing one DNA chain has been found to be »62 for the 2000bp DNA, which is larger than the corresponding experimental value of 35 dendrimers for salmon sperm DNA. For the longer DNA,  is estimated to »135, which is very close to the corresponding experimental value of 140 dendrimers for a linearized T7 DNA plasmid. From the results for the shorter DNA, of the wrapping length and the maximum number of dendrimers per one DNA molecule, it is concluded that the dendrimer is overcharged, with an effective charge of -19.5 e. This means that charge inversion occurs for the dendrimer in this case, but this is not observed for the longer DNA, where the complex has an effective charge of +5.8 e.

Keywords: nanostructures,  DNA, G4 dendrimers, dendrimer-DNA complex, wrapping length.

Corresponding author  contact: Khawla Qamhieh, Al-Quds Uiversity,                           Fax: 00972-2-2796960, Tel: 00972-2-2799753, E-mail: khawlaqa@yahoo.com