The characterization of a novel dendritic system for gene delivery by isothermal titration calorimetry.
Understanding the nature of binding of polycationic dendrimers to DNA provides useful information on their role in gene delivery. In the present study, we have characterized the interaction of several peptide-based polycationic dendrimers with salmon sperm DNA using isothermal titration calorimetry. The dendrimers consisted of the cell penetrating peptide TAT, a nuclear localization signal peptide and dendritic polylysine. The binding affinity and thermodynamic parameters were found to increase as the number of positive charges on the dendrimer increased, indicating that ionic interactions were the major binding forces between the two molecules. The effect of acidic pH (3.2) compared to a more neutral pH (7.2) was also examined. The binding affinity was stronger at the lower pH but precipitation of the complex was more prominent at pH 7.2 which was shown by large enthalpies. The results indicate that our dendrimers are forming stable complexes with DNA.
Coles
Daniel J
DJ
School of Molecular and Microbial Sciences, The University of Queensland, St Lucia, Qld 4072, Australia.
Yang
Shu
S
Minchin
Rodney F
RF
Toth
Istvan
I
D000818:Animals; D001665:Binding Sites; D002151:Calorimetry; D004247:DNA / Q000008:administration & dosage* / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006863:Hydrogen-Ion Concentration; D008297:Male; D012474:Salmon / Q000235:genetics; D013696:Temperature; D017186:Titrimetry
D050091:Dendrimers; D004247:DNA