Addition of poly (propylene glycol) to multiblock copolymer to optimize siRNA delivery

Dai, Zhi; Arévalo, Maria T; Li, Junwei; Zeng, Mingtao

The effectiveness of our siRNA-bound complexes may be explained by their physical, structural, and chemical characteristics. P2-siRNA complex was larger in size and had a greater surface charge. A higher cationic charge in the complexes corresponds to higher transfection efficiency, and is favorable for . Particle size of complexes of copolymer P1, P2, and P3 with GFP siRNa at various N/P ratios. copolymer-siRNa complexes were prepared in aqueous solution using multiple N/P ratios while keeping siRNa (200 pmol) constant. sizes were determined at 25 °c using the Zetasizer Nano. intracellular release of siRNA. While this higher cationic charge of P2 complex may induce greater gene knockdown, it may also induce greater cytotoxicity. In contrast, for P3-siRNA complex, greater gene knockdown may be attributed to the PPG structure of copolymer P3 and the micelle-complex architecture of their aggregates. In addition, while copolymers P1 and P2 are water soluble block copolymers that can complex with siRNA to form micelle-like aggregates of larger size and lesser density, copolymer P3 has hydrophobic block PPG units. It is possible that the copolymer P3-siRNA complex entered the cells more readily because of its small volume and dense architecture as compared with P1and P2-siRNA complexes.