Non-covalent Nanocomplexes of Folic Acid and Reducible Polyethylenimine for Survivin siRNA Delivery

Abstract

Background/aim: Efficient delivery of siRNA is critical for its therapeutic applications. This study was aimed at the design, synthesis and evaluation of a novel delivery system based on non-covalent complexes of folic acid (FA) and a reducible polyethylenimine (PEI) derivative, PEI-SS.

Materials and methods: PEI-SS was synthesized by crosslinking low-molecular weight PEI using a reducible crosslinking agent. PEI-SS-siRNA complexes were synthesized and further combined with FA to form FA/PEI-SS-siRNA nanocomplexes. These were then evaluated in two tumor cell lines for survivin siRNA delivery.

Results: FA/PEI-SS-siRNA complexes were taken-up by both HeLa and A549 cells efficiently. This was not affected by the expression level of the folate receptor on the tumor cell surface. Furthermore, FA/PEI-SS-siRNA complexes reduced the level of survivin expression in both cell lines.

Conclusion: FA/PEI-SS is a potent siRNA carrier that warrants further evaluation.

Keywords: Polyethylenimine; cancer; drug delivery; folate receptor; nanoparticle; siRNA.