Ratio of Polycation and Serum Is a Crucial Index for Determining the RNAi Efficiency of Polyplexes

We report that the mass ratio of the polycation to serum in the medium determines the (RNA interference) RNAi efficiency in vitro by using spermine-modified pullulan (Ps) and spermine-modified dextran (Ds) as polycation models. The high ratio of Ps to serum protein (Ps/Pr) mediated the formation of larger polyplexes, which led to the promoted cellular uptake, enhanced lysosomal escape, and elevated RNAi efficiency. In addition, the supplementary of free Ps also enhanced small interfering RNA transfection because of the elevation of Ps/Pr. Similar results were obtained with Ds. Compared with the adjustment of the nitrogen to phosphate (N/P) ratio in the polyplex, these findings revealed a more applicable strategy to tune the polycation-mediated RNAi efficiency in the serum-containing culture medium.