Poly(propyleneimine) dendrimers as potential siRNA delivery nanocarrier: from structure to function

Abstract

The goal of the present investigation is to reveal the role of the Poly(propyleneimine) (PPI) dendrimer structure on the siRNA nanoparticles formation, facilitation of cell internalisation, and sequence specific knockdown of targeted genes. It was found that the higher generations of PPI dendrimers (G4 and G5) most effectively initiated the complexation of siRNA into discrete nanoparticles when compared with lower generations of dendrimers (G2 and G3) as determined by tapping mode atomic force microscopy and dynamic light scattering. The formulated siRNA-PPI dendrimer complexes provided for a dramatic enhancement in siRNA cellular internalisation and the marked knockdown of targeted mRNA expression in A549 human lung cancer cells. While the size and positive charge density of G5 is much larger than G4 dendrimers, provoking higher toxicity, G4 dendrimer shows the maximum efficacy terms of siRNA nanoparticles formation, intracellular siRNA internalisation, and sequence specific gene silencing.