Jensen, Linda B and Mortensen, Kell and Pavan, Giovanni Maria and Kasimova, Marina R and Jensen, Ditte K and Gadzhyeva, Veronika and Nielsen, Hanne M and Foged, Camilla (2010) Molecular characterization of the interaction between siRNA and PAMAM G7 dendrimers by SAXS, ITC, and molecular dynamics simulations. Biomacromolecules, 11 (12). pp. 3571-3577. ISSN 1525-7797
Full text not available from this repository.Abstract
A prerequisite for the use of dendrimers as drug delivery vehicles is the detailed molecular understanding of the drug interaction. The purpose of this study was to characterize the self-assembly process between siRNA and generation 7 poly(amidoamine) dendrimers and the resulting dendriplexes in aqueous solution using structural and calorimetric methods combined with molecular dynamics simulations. Complexes with a length scale of 150 nm showed a decreasing size with increasing amine-to-phosphate ratio by dynamic light scattering. At the molecular level, individual dendrimers studied by small-angle X-ray scattering (SAXS) showed no change in size upon siRNA binding, suggesting a rigid sphere behavior. Isothermal titration calorimetry (ITC) demonstrated exothermic binding with a concentration-dependent collapse of complexes. Both the experimentally determined ΔH(bind) and size were in close accordance with molecular dynamics simulations. This study demonstrates the unique complementarity of SAXS, ITC, and modeling for the detailed description of the molecular interactions between dendrimers and siRNA during dendriplex formation.
| Item Type: | Scientific journal article, Newspaper article or Magazine article |
|---|---|
| Subjects: | Physical sciences > Chemistry |
| Depositing User: | Giovanni Maria Pavan |
| Date Deposited: | 23 Aug 2016 07:35 |
| Last Modified: | 23 Aug 2016 07:35 |
| URI: | http://repository.supsi.ch/id/eprint/7611 |
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