AS1411 Aptamer Conjugated Gelatin-Siloxane Nanoparticles for targeted siRNA delivery

Abstract

RNA interference (RNAi) has potential advantages over other gene therapy approaches due to its high specificity and the ability to inhibit target gene expression. Thus, developing a stable, safe, effective siRNA delivery system is necessary to achieve targeted therapy. Here, we developed such a system by conjugating gelatin-based nanoparticles with the nucleolin-targeted AS1411 aptamer and siRNA sequence together (Apt-GS/siRNA NPs) via a disulphide linker. These Apt-GS/siRNA NPs demonstrated favourable release of siRNA under reducing conditions owing to disulphide cleavage. Furthermore, the Apt-GS/siRNA NPs could selectively deliver siRNA to A549 cells overexpressing nucleolin via a nucleolin-mediated transmembrane process, subsequently resulting in efficient RNAi. These results indicated that the Apt-GS/siRNA NPs could facilitate nucleolin-targeted siRNA delivery and gene silencing in tumours.