Enhancing Gene Knockdown Efficiencies by Comparing siRNA-Loaded Cationic Nanogel Particles of Different Sizes

Abstract

In order to silence the expression levels of pathogenic genes, small interfering RNA (siRNA) requires a nano-sized carrier for its safe and stable delivery into cells. In this research highlight, we focus on well-defined cationic nanohydrogel particles developed in our group for such purposes. To investigate the nanogels’ mechanism for enhanced knockdown efficiencies, we recently synthesized two sets of particles with similar material composition and siRNA-loading characteristics, but – according to the manufacturing process – of different sizes. Within this study, 100-nm-sized nanogel particles loaded with siRNA accumulated inside the lysosomes already after 4 h and could not induce any gene knockdown, while 40-nm-sized particles were able to avoid lysosomal accumulation, and instead, generated moderate gene knockdown levels lasting for about three days. We believe that in analogy to other reports this size-dependent intracellular distribution behavior might be an essential key parameter for tuning the knockdown efficiency of the nanogel carriers. Moreover, these results might further contribute to the development of advanced siRNA carrier systems in order to enhance RNAi’s translation into the clinics.