Study of non-covalent interactions on dendriplex formation: Influence of hydrophobic, electrostatic and hydrogen bonds interactions.

The interaction of a double stranded small interference RNA (siRNA Nef) with cationic carbosilane dendrimers of generations 1-3 with two different ammonium functions at the periphery ([-NMe2R]+, R=Me, (CH2)2OH) has been studied by experimental techniques (zeta potential, electrophoresis, single molecule pulling experiments) and molecular dynamic calculations. These studies state the presence of different forces on dendriplex formation, depending on generation and type of ammonium group. Whilst for higher dendrimers electrostatic forces mainly drive the stability of dendriplexes, first generation compounds can penetrate into siRNA strands due to the establishment of hydrophobic interactions. Finally, in the particular case of first generation dendrimer [G1O3(NMe2(CH2)2OH))6]6+; the presence of hydroxyl groups reinforces dendriplex stability by hydrogen bonds formation. However, since these small dendrimers do not cover the RNA, only higher generation derivatives protect RNA from degradation.