Effective RNAi in leukemia cells is enhanced by spermine-modified pullulan combined with desloratadine

RNA interference is a very useful tool for clinical treatment as well as mechanistic studies of leukemia. However, leukemia cells are known as hard-to-transfected by non-virus carriers. The low capacity of endocytosis and lysosomal escape of synthetic carriers are two obstacles for successful RNAi in leukemia cells. In this work, we established a universal powerful strategy for mediating effective RNAi in different types of leukemia cells by sequentially using spermine-modified pullulan (PS) as siRNA carrier and desloratadine (DL) to promote the lysosomal escape. It was shown that the complex of PS and siRNA could be largely internalized by human T-cell acute lymphoblastic leukemia cells, acute myeloid leukemia cells and chronic myeloid leukemia cells in serumcontaining media, and the internalized complex was able to escape from the lysosomes by the aid of DL, resulting in effective RNAi against the key genes for the different leukemia cells.

Automated summary

This study established a universal strategy for effective RNA interference in different types of leukemia cells by using PS as an siRNA carrier and DL to promote lysosomal escape. The complex of PS and siRNA could be internalized by leukemia cells and escape from lysosomes with the aid of DL, resulting in effective RNAi against key genes.