HA-Modified R8-Based Bola-Amphiphile Nanocomplexes for Effective Improvement of siRNA Delivery Efficiency.

The development of new nonviral vectors with high transfection efficiency and low cyto-toxicity remains a great challenge in the field of small interfering RNA delivery. To address the challenge, we developed two cationic amphiphilic carriers, octa-arginine double-substituted (R8-bibola) and octa-arginine monosubstituted (R8-monobola), based on transmembrane peptide-octa-arginine (R8) for complexing siRNA (R8-bola/siRNA). To further improve the stability of the nanocomplexes and tumor targeting, HA-R8-bola/siRNA nanocomplexes were prepared by surface modification of R8-bola/siRNA with hyaluronic acid (HA). In vitro experiments showed that R8-bibola has better biocompatibility than R8-monobola, which effectively increased the cell uptake of siRNA and improved the Bcl-2 protein silencing efficiency. In vivo antitumor experiments confirmed that the HA-modified nanocomplexes effectively inhibited tumor growth by silencing Bcl-2 protein expression. The new bola-type nanoparticles provide a new strategy to improve the delivery efficiency of siRNA for tumor treatment.