Less is more – multiscale modelling of self-assembling multivalency and its impact on DNA binding and gene delivery

• DOI: 10.1039/c0sc00291g
• Publication Date: 2010-07-09T08:30:38Z
• Authors: Paola Posocco; Sabrina Pricl; Simon Jones; Anna Barnard; David K. Smith
• Keywords: drug delivery; dendron; computer-assisted molecular simulation; drug delivery; computer-assisted molecular simulation; dendrons; nucleic acid; 01 natural sciences; nucleic acid; 0104 chemical sciences

This edge article reports the multiscale modelling of spermine-functionalised dendrons designed to bind DNA and deliver it into cells. The modelling provides an insight into the mode of self-assembly of the dendrons, in particular aggregate charge density and shape, and hence suggests explanations for some of the unexpected experimental observations. In particular, the self-assembly model helps explain why the first generation dendron is more effective in binding DNA than the second generation analogue, even though the second generation system has a greater number of surface spermine ligands. Effective self assembly of the first generation dendron leads to a high charge density assembled structure – more effective than the larger number of ligands on the second generation dendron – i.e., less is more. The modelling also suggests an alternative shape of self-assembly for the system with two hydrophobic cholesterol units (rather than one) at the dendron focal point – this may help explain why this system shows much enhanced gene delivery in vitro.