Synthesis and Characterization of Quaternized Poly(β-amino ester) for Highly Efficient Delivery of Small Interfering RNA.

The development of non-viral vectors for gene delivery has gained attention over the past decades. Specifically, poly(β-amino ester) (PBAE) has shown great potential for improving the delivery of gene therapeutics. It has been observed that low-molecular-weight PBAE displayed low transfection activities, while quaternization could enhance the transgene expression efficacy of PBAE. Herein, PBAE quaternary ammonium salt (PBAEQAS) was synthesized to increase the positive charge of the polymers, which resulted in an increase in siRNA binding efficiency based on self-assembly electrostatic interaction. Specifically, the nanoparticle surface was positively charged, which increased the uptake ability of siRNA. Compared with acrylate-PBAEQAS/siNC nanoparticles and amine-PBAEQAS/siNC nanoparticles, acrylate-PBAEQAS/siSurvivin nanoparticles and amine-PBAEQAS/siSurvivin nanoparticles induced more-efficient cell apoptosis and gene silencing. All these results suggest that PBAEQAS would be a promising gene delivery vector for cancer treatment.